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Interaction between the actions of taurine and angiotensin II
Abstract
The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immunodeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin II on Ca2+ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably very important.
... In this case, viral cell entry would not solely depend on surface ACE2 expression, but also on its endocytosis induced by Ang II-AT 1 R signaling. Taurine has previously been shown to upregulate mACE2 -albeit its magnitude still unknown -and attenuate the actions of Ang II (Lv et al. 2017;Schaffer et al. 2000). Taurine may therefore, in theory, impede viral cell entry by attenuating AT 1 R-mediated endocytosis of the SARS-CoV-2/ACE2 complex, thereby preserving ACE2 protective functions, primarily by converting Ang II to Ang1-7. ...
... This hypothesis is supported by a study in which increased levels of taurine were measured in peripheral blood mononuclear cells (PBMCs), where it can neutralize HOCl, thereby favoring anti-oxidation and anti-inflammation (Chorazy et al. 2002;Singh et al. 2021b). Other proinflammatory mediators have been shown to be inhibited by taurine, including Ang II, AT 1 R, TLR4, IL-1β, NADPH oxidase, and the NLRP3inflammasome (Han et al. 2016;Liu et al. 2019;Schaffer et al. 2000;Younis et al. 2021). At the same time, taurine can increase anti-inflammatory ACE2 and Ang(1-7), in addition to IL-10 (Lv et al. 2017;Schaffer et al. 2000). ...
... Other proinflammatory mediators have been shown to be inhibited by taurine, including Ang II, AT 1 R, TLR4, IL-1β, NADPH oxidase, and the NLRP3inflammasome (Han et al. 2016;Liu et al. 2019;Schaffer et al. 2000;Younis et al. 2021). At the same time, taurine can increase anti-inflammatory ACE2 and Ang(1-7), in addition to IL-10 (Lv et al. 2017;Schaffer et al. 2000). Supplementation dosages vary greatly across human studies reporting on the effect of taurine supplementation on inflammatory markers. ...
Taurine is an amino sulfonic acid that is implicated in numerous physiological functions, including the regulation of oxidative stress, which plays an important role in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), together with other pathophysiological processes. The recent finding of decreased serum taurine levels in SARS-CoV-2-infected patients, in tandem with its potential modulatory role in COVID-19 due to its antiviral, antioxidant, anti-inflammatory, and vascular-related effects, provides a rationale for considering taurine as a beneficial supplement in patients suffering from COVID-19. Here, we reviewed the potential disease-modifying effects of taurine and combined these with the current knowledge on COVID-19 to clarify the potential role of taurine in this respiratory disease.
... Часто даже при назначении комбинации препаратов основных рекомендованных классов не удается достичь должного результата, что послужило основанием для поиска новых лекарственных средств, обладающих выраженной активностью на метаболическом уровне, -препараты с антигипоксантной и антиоксидантной фармакологической направленностью, относящиеся к корректорам метаболизма или цитопротекторам. Среди них особый интерес представляет сульфоаминокислота таурин, играющая роль естественного антагониста кальция в кардиомиоците [11], физиологического ингибитора ангиотензина II [12], эндотелиотропного средства, положительно влияющего на реактивность сосудов, эндотелиальный апоптоз, выраженность окислительного стресса и воспаления, связанных в первую очередь с диабетом [13,14]. Кроме того, в эксперименте таурин продемонстрировал гепатопротекторные свойства при НАЖБП [15], экспериментальном стеатозе печени [16], фиброзе печени [17], СД и его осложнениях [18,19]. ...
... Установленное в ходе исследования благоприятное влияние таурина на функциональные показатели, характеризующие синдром цитолиза и холестаза, по-видимому, обусловлено возможностью таурина подавлять опосредованный свободными жирными кислотами апоптоз и стресс эндоплазматического ретикулума при экспериментальном стеатозе печени [16], доказанными антиоксидантными и противовоспалительными свойствами таурина [12,24]. Кроме того, результаты экспериментального исследования С.Gentile и соавт. ...
... ДД 3-й степени, выявленная при первичном обследовании, не встретилась в обеих группах по окончании 16-недельной терапии. По-видимому, положительное влияние таурина на течение ХСН обусловлено не только доказанными антиоксидантными и противовоспалительными свойствами таурина, но и способностью нивелировать эффекты ангиотензина II, а соответственно, снижать скорость прогрессирования ремоделирования ЛЖ [12]. Кроме того, у пациентов, принимавших таурин в составе комбинированной терапии, отмечено уменьшение содержания маркера синтеза коллагена I типа, специфичного для фиброза сердца, с 92,5±2,7 до 81,4±2,3 нг/мл (D%=-13,5) vs 94,6±2,5 до 89,7±3,2 (D%=-5,46) во 2-й группе, что может свидетельствовать об уменьшении прогрессирования образования фиброза в сердце под влиянием таурина. ...
... Таурин виявляє кардіопротекторні ефекти за перорального введення, як це показано в дослідах на щурах Wistar протягом 30 днів після ішемії, спричиненої оклюзією коронарної артерії [29]. Ці тварини мали знач но менший розмір інфаркту міокарда, підвищену активність супероксиддисмутази та зниження рівня запальних маркерів інтерлейкіну (IL)-6 і фактора некрозу пухлин альфа (TNF-α) порівняно з контрольною групою [29]. ...
... Таурин виявляє кардіопротекторні ефекти за перорального введення, як це показано в дослідах на щурах Wistar протягом 30 днів після ішемії, спричиненої оклюзією коронарної артерії [29]. Ці тварини мали знач но менший розмір інфаркту міокарда, підвищену активність супероксиддисмутази та зниження рівня запальних маркерів інтерлейкіну (IL)-6 і фактора некрозу пухлин альфа (TNF-α) порівняно з контрольною групою [29]. Це наводить на думку, що добавки таурину можуть бути ефективним підходом до реалізації принципів кардіозахисту. ...
Мета дослідження – оцінити на прикладі амінокислот можливість використання комбінацій активних субстанцій – аналогів природних метаболітів, а також розглянути та ідентифікувати нові потенційні фармакологічні мішені їхньої дії. Комбінування діючих речовин – добре відомий метод створення лікарських засобів. Однак деякі лікарські препарати та нутрицевтики, які широко застосовуються та містять пероральні форми карнітину, холіну, ерготеїну, фосфоліпідів, лецитину та ін., можуть сприяти виникненню чи посилювати розвиток серцево-судинної патології та її ускладнень. Це необхідно враховувати та відображати в Інструкції з медичного застосування. Крім того, наводяться дані щодо можливості усунення небажаних ефектів, зокрема, на прикладі використання аргініну як прекурсору оксиду азоту, сірковмісною кислотою таурином. Розкриваються механізми синергічного впливу даної комбінації на ендотеліальну функцію судин і системні ефекти загалом, при нівелюванні можливої негативної дії аргініну. Таким чином, комбіноване застосування нутрицевтиків з однаковим позитивним впливом на патогенетичні ланки захворювання та здатністю послаблювати можливі негативні ефекти один одного може бути новою стратегією раціонального створення комбінованих засобів, що показано на прикладі комбінації аргініну та таурину.
... The effects of TAU in decreasing blood pressure (BP) are another interesting feature of this compound [210,211] (Fig. 1). An important mechanism for the antihypertensive properties of TAU is mediated through its effects on the reninangiotensin system [221]. It has been found that TAU could significantly attenuate the vaso-constrictive properties of angiotensin II [221] (Fig. 1). ...
... An important mechanism for the antihypertensive properties of TAU is mediated through its effects on the reninangiotensin system [221]. It has been found that TAU could significantly attenuate the vaso-constrictive properties of angiotensin II [221] (Fig. 1). The effect of TAU on the renal system of kinin-kallikrein could also play a role in its antihypertensive properties [222,223]. ...
It is well-known that taurine (TAU) concentration in the excitable tissues such as the myocardium is exceptionally high (up to 30 mM). TAU accumulation in the cardiomyocytes is a transporter-mediated process. Therefore, this amino acid should play a critical role in cardiac tissue. Several studies revealed that a decrease in cardiac TAU could lead to atrophic cardiomyopathy and impaired cardiac function. At subcellular levels, the effects of TAU on mitochondria and energy metabolism are an essential part of its function in the heart. Besides, it has been found that exogenous TAU supplementation significantly enhanced cardiac mitochondrial function and ATP levels. In the current chapter, the effects of TAU on cardiovascular diseases linked with mitochondrial impairment are highlighted, and the role of TAU as a cardioprotective agent is discussed. The data collected here could provide clues in managing a wide range of cardiovascular complications connected with the energy crisis and mitochondrial dysfunction.
... The renin-angiotensin system plays a pivotal role in the homeostasis of arterial pressure, body fluids and electrolyte balance, and activation of the renin-angiotensin system contributes to hypertension in several animal models (Putnam et al. 2012). Taurine reduces cardiac hypertrophic effects of angiotensin II in adult rats (Schaffer et al. 2000). In contrast, taurine deficiency in mature animals exacerbates many of the adverse actions of angiotensin II on the heart, blood vessels and kidneys (Cruz et al. 2000). ...
... Perinatal taurine supplementation prevents hypertension in spontaneously hypertensive rats, likely, in part, by an antioxidant effect (Racasan et al. 2004). In addition, taurine inhibits the renin-angiotensin system (Schaffer et al. 2000), reduces cytokine and endothelin levels (Hu et al. 2009) and suppresses norepinephrine release from the peripheral sympathetic nerves (Hano et al. 2009). These perinatal alterations may underlie the perinatal effect of taurine and then program adult cardiovascular function and hypertension. ...
Taurine is an abundant, free amino acid found in mammalian cells that contributes to many physiologic functions from that of a simple cell osmolyte to a programmer of adult health and disease. Taurine's contribution extends from conception throughout life, but its most critical exposure period is during perinatal life. In adults, taurine supplementation prevents or alleviates cardiovascular disease and related complications. In contrast, low taurine consumption coincides with increased risk of cardiovascular disease, obesity and type II diabetes. This review focuses on the effects that altered perinatal taurine exposure has on long-term mechanisms that control adult arterial blood pressure and could thereby contribute to arterial hypertension through its ability to program these cardiovascular regulatory mechanisms very early in life. The modifications of these mechanisms can last a lifetime and transfer to the next generation, suggesting that epigenetic mechanisms underlie the changes. The ability of perinatal taurine exposure to influence arterial pressure control mechanisms and hypertension in adult life appears to involve the regulation of growth and development, the central and autonomic nervous system, the renin-angiotensin system, glucose-insulin interaction and changes to heart, blood vessels and kidney function.
... Growing evidence suggest that reduced NO signalling, 15 increased sympathetic tone, 37 upregulation of angiotensin AT 1 receptors and stimulation of sodium transporters 38 contribute to hypertension induced by chronic BSO treatment. Conversely, taurine has been shown to suppress the sympathetic nervous system, 39 block the effects of angiotensin (Ang) II 40 and modulate intracellular and extracellular concentrations of sodium. 41 In the present study, taurine treatment resulted in significant decreases in IRV and SR concomitant with recovery of GSH and reductions in blood pressure in BSO-treated rabbits, suggesting that taurine may reduce oxidatively accelerated neointimal hyperplasia by enhancing GSH biosynthesis. ...
... 42 Both explanations seem plausible because taurine is indirectly involved in GSH biosynthesis in the liver 43 and blocks the effects of AngII. 40 However, a significant decrease in the amount of neointimal hyperplasia was also evident in the taurine group in the present study, which exhibited no significant differences in either mean GSH levels or blood pressure compared with the placebo group. This raises the question as to whether the inhibitory action of taurine on neointimal hyperplasia may be related to its local effects on the balloon-injured area. ...
1. In endothelial cells, the major receptor for the binding and internalization of oxidized low‐density lipoprotein (LDL) is the lectin‐like oxidized LDL receptor (LOX‐1). The aim of the present study was to investigate the effects of taurine on intimal thickening and LOX‐1 expression under normal and oxidative conditions.
2. The iliac artery of rabbits were subjected to balloon injury and oxidative stress was induced by 14 days treatment of rabbits with 75 mg/kg, s.c., buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis. Taurine was administered in drinking water (1%, w/v) for 14 days in the presence (BSO + Taurine group) and in the absence of BSO treatment (Taurine group). In taurine and placebo groups, rabbits were injected with 4 mL, s.c., 0.9% NaCl (vehicle for BSO) for 14 days.
3. Taurine (1% in drinking water, w/v) preserved plasma levels of anti‐oxidants and lowered the increased blood pressure induced by BSO. The stenosis rate of 29.92% in the placebo group increased to 72.20% in the BSO group, which was significantly reduced to 42.21% by taurine ( P < 0.001; n = 5). Localization of LOX‐1 to the intima and media of the iliac artery was demonstrated in the present study. Taurine treatment reduced the BSO‐induced increase in LOX‐1 expression at both the protein and mRNA levels ( P < 0.05 and P < 0.01, respectively).
4. The results demonstrate that the stenosis rate and LOX‐1 expression correlate well with oxidative status. Manipulation of LOX‐1 expression by taurine may have therapeutic benefits in preventing restenosis.
... On the other hand, taurine has been shown to be renoprotective in various models (Han and Chesney, 2012). Also, taurine facilitates natriuresis and diuresis through mediating renal osmoregulatory activity (Schaffer et al., 2000). TCM and pharmacology studies have shown pulmonary function to be linked closely to kidney function, taking part together in modulating fluid-water balance (Malek et al., 2018). ...
Background: Descurainia sophia seeds (DS) is a herbal medicine in traditional Chinese medicine (TCM) for treating lung diseases. We aimed to evaluate the therapeutic effect of DS and five of its fractions upon pulmonary edema (PE) through metabolomics analysis (MA) of urine and serum samples of rats.
Methods: A PE model was established by intrathoracic injection of carrageenan. Rats were pretreated with DS extract or its five fractions (polysaccharides (DS-Pol); oligosaccharides (DS-Oli); flavonoid glycosides (DS-FG); flavonoid aglycone (DS-FA); fat oil fraction (DS-FO)) for seven consecutive days. Forty-eight hours after carrageenan injection, lung tissues were subjected to histopathology. MA of urine and serum was done by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, respectively. Principal component analysis and orthogonal partial least squares-discriminant analysis were operated for the MA of rats and potential biomarkers related to treatment. Heatmaps and metabolic networks were constructed to explore how DS and its five fractions act against PE.
Results: DS and its five fractions could all attenuate pathologic lung injury to different degrees, and DS-Oli, DS-FG, and DS-FO had a more potent effect compared with DS-Pol and DS-FA. DS-Oli, DS-FG, DS-FA, and DS-FO could regulate the metabolic profiles of PE rats, but DS-Pol was less potent. According to MA, the five fractions could improve PE to some degree due to their anti-inflammatory, immunoregulatory, and renoprotective activities by mediating the metabolism of taurine, tryptophan, and arachidonic acid. However, DS-Oli, DS-FG, and DS-FO had more important roles in edema-fluid reabsorption, and reduction of vascular leakage through regulating the metabolism of phenylalanine, sphingolipid and bile acid. Finally, heatmaps and hierarchical clustering analysis indicated DS-Oli, DS-FG, and DS-FO to be more efficacious than DS-Pol or DS-FA against PE. The five fractions of DS had a synergistic effect on PE from different aspects, thereby constituting the entire efficacy of DS. DS-Oli, DS-FG, or DS-FO could be used as an alternative to DS.
Conclusion: MA combined with use of DS and its fractions provided novel insights into the mechanism of action of TCM.
... Exposure of cardiomyocytes to high glucose leads to functional and structural abnormalities that can be prevented by linoleic acid preconditioning and partially mediated activation of peroxisome proliferator-activated receptor γ (Aloud et al., 2016). Studies have shown that taurine can be involved in the regulation of angiotensin II (Schaffer et al., 2000)and pyruvate dehydrogenase (Hansen, 2001) to exert cardioprotective effects. The present study demonstrated that naringin protected cardiomyocytes from hyperglycemia-induced injury in vitro by upregulating KATP channels and inhibiting NF-κB pathway (You et al., 2016). ...
Background : Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as Diabetic cardiomyopathy (DCM). However, potential targets and molecular mechanisms remain unclear. Therefore, our research was designed to evaluate rat myocardial morphology, fat metabolism and oxidative stress to verify myocardial protective effect of YP-SJ formula in vivo . And then to explore and validate its probable mechanism through network pharmacology and experiments in vitro and in vivo .
Methods: In this study, DCM rats were randomly divided into five groups: control group, model group, and three YP-SJ formula groups (low-dose, middle-dose, and high-dose groups). Experimental rats were treated with 6 g/kg/d, 12 g/kg/d and 24 g/kg/d YP-SJ formula by gavage for 10 weeks, respectively. Cardiac function of rats was measured by high-resolution small-animal imaging system. The cells were divided into control group, high glucose group, high glucose + control serum group, high glucose + dosed serum group, high glucose + NC-siRNA group, high glucose + siRNA-FoxO1 group. The extent of autophagy was measured by flow cytometry, immunofluorescence, and western blotting.
Results: It was found that YP-SJ formula could effectively improve cardiac systolic function in DCM rats. We identified 46 major candidate YP-SJ formula targets that are closely related to the progression of DCM. Enrichment analysis revealed key targets of YP-SJ formula related to environmental information processing, organic systems, and the metabolic occurrence of reactive oxygen species. Meanwhile, we verified that YP-SJ formula can increase the expression of forkhead box protein O1 (FoxO1), autophagy-related protein 7 (Atg7), Beclin 1, and light chain 3 (LC3), and decrease the expression of phosphorylated FoxO1 in vitro and in vivo . The results showed that YP-SJ formula could activate the FoxO1 signaling pathway associated with DCM rats. Further experiments showed that YP-SJ formula could improve cardiac function by regulating autophagy.
Conclusion: YP-SJ formula treats DCM by modulating targets that play a key role in autophagy, improving myocardial function through a multi-component, multi-level, multi-target, multi-pathway, and multi-mechanism approach.
... Due to their complex formulations, both negative and positive effects on BBB integrity may be realized with regular, significant consumption of energy drinks. Evidence consistent with the latter are findings that energy drinks can have acute hypertensive effects on blood pressure, but paradoxically, hypotensive effects with chronic ingestion (11)(12)(13)(14)(15)(16)(17). Chronic consumption of sugar-formulated energy drinks may also have secondary indirect neurovascular effects, exacerbating hyperglycaemia, insulin resistance (18)(19)(20)(21)(22) and neurovascular integrity and neuroinflammation (23)(24)(25). ...
Energy drinks containing significant quantities of caffeine and sugar are increasingly consumed, particularly by adolescents and young adults. Chronic ingestion of energy drinks may potentially regulate vascular risk factors. This study investigated the effects of chronic ingestion of energy drinks on blood-brain barrier (BBB) integrity and neuroinflammation. Male C57BL/6J mice were maintained on water (control), MotherTM (ED), sugar-free MotherTM (sfED), or Coca ColaTM soft drink (SD) for 13 weeks. The BBB integrity and neuroinflammation were analyzed with semi-quantitative immunofluorescent microscopy. Blood pressure, plasma inflammatory cytokine levels and blood glucose were also considered. Following 13 weeks of intervention, mice treated with ED, sfED, and SD showed significant disruption of BBB. However, marked neuroinflammation was observed only in sfED group mice. The consumption of ED and sfED significantly altered the blood pressure and plasma concentrations of inflammatory cytokines, TNF-a, IL-4, IL-6, and IL-10, and both increased plasma glucose. Correlation analyses showed significant associations between BBB dysfunction and hypotension, hyperglycaemia and cytokine dyshomeostasis. The intake of energy drink, particularly the sugar free formulation, may compromise the integrity of BBB and induce neuroinflammation via hypotension, hyperglycaemia and inflammatory pathways.
... The primary ingredients of popular energy drinks such as Red Bull TM , Mother TM , and Monster TM are caffeine/guarana (160 mg/serve), taurine, (2000 mg/serve), B6/B12 vitamins (1.0 mg/0.5 µg/serve respectively), sugar (51 g/serve), or alternative artificial sweeteners (e.g., sucralose and acesulfame potassium (Ace-K)) [11]. Clearly, consumption of energy drinks is relevant to risk for and severity of metabolic syndrome, because of interactive potential effects via increased provision of energy from diet and subsequent adiposity [12], a consequence of changes in energy utilisation patterns [13][14][15][16], potential effects on blood-pressure and vascular tone [17][18][19][20][21][22], a consequence of potential changes in vascular architecture (e.g., advanced glycation end-products) [23][24][25], or exacerbation of endocrine disorders (hyperinsulinemia/insulin resistance) [26][27][28][29][30]. However, there is no current literature exploring potential chronic interactive effects of energy drinks on metabolic syndrome. ...
Energy drinks containing significant quantities of caffeine, taurine and sugar are increasingly consumed, particularly by adolescents and young adults. The putative effects of chronic ingestion of either standard energy drink, MotherTM (ED), or its sugar-free formulation (sfED) on metabolic syndrome were determined in wild-type C57BL/6J mice, in comparison to a soft drink, Coca-Cola (SD), a Western-styled diet enriched in saturated fatty acids (SFA), and a combination of SFA + ED. Following 13 weeks of intervention, mice treated with ED were hyperglycaemic and hypertriglyceridaemic, indicating higher triglyceride glucose index, which was similar to the mice maintained on SD. Surprisingly, the mice maintained on sfED also showed signs of insulin resistance with hyperglycaemia, hypertriglyceridaemia, and greater triglyceride glucose index, comparable to the ED group mice. In addition, the ED mice had greater adiposity primarily due to the increase in white adipose tissue, although the body weight was comparable to the control mice receiving only water. The mice maintained on SFA diet exhibited significantly greater weight gain, body fat, cholesterol and insulin, whilst blood glucose and triglyceride concentrations remained comparable to the control mice. Collectively, these data suggest that the consumption of both standard and sugar-free forms of energy drinks induces metabolic syndrome, particularly insulin resistance.
... Additionally, ability to decrease blood pressure of these digested meats may be come from taurine which is a neutral β-amino acid derived from the metabolism of Sulphur containing amino acids. The Main mechanism through which taurine may decrease blood pressure is thought to be the attenuation of angiotensin II signaling, which causes vasoconstriction and consequently increases blood pressure [42]. Taurine may also reduce blood pressure through enhancement of the kinin-kallikrein system in the kidney that causes vasodilation [43] and may also lower blood pressure by decreasing levels of epinephrine (which increases heart rate) and norepinephrine (which causes vasoconstriction) [44]. ...
... Elevated blood pressure lipid profile by increasing LDL receptor upregulation and LDL uptake into the liver [13,14]. ...
... Thus, this aspect of taurine should be challenged in the future by demonstrating its direct anti-oxidant properties if there are any. In addition, since most studies reporting an anti-oxidant-like effect of taurine were done in conditions that mimic cardiac pathologies such as Ang II-induced hypertrophy (Takahashi et al. 1997;Azuma et al. 2000;Schaffer et al. 2000;Xu et al. 2008), the question is oes taurine have an anti-oxidant-like effect in nonpathological conditions? Hence, as it stands, according to the current literature in the field, the effect of taurine on ROS seems to be indirect and depends on the type of pathology under study. ...
Taurine is a non-essential amino acid that has received much attention. Two organs, the heart, and the brain, are known to produce their own taurine, but in very limited quantities. It is for this reason that supplementation with this amino acid is necessary. Today, taurine is present in almost all energy drinks. A very vast literature reported beneficial effects of taurine in hepatic dysfunction, gastrointestinal injury, kidney diseases, diabetes, and cardiovascular diseases. Most of its effects were attributed to its modulation of Ca2+ homeostasis as well as to its antioxidant properties. In this review, we will focus on the current status of taurine modulation of the cardiovascular system and discuss future avenues for its use as a supplement therapy in a specific cardiovascular disease, namely hypertrophy, and heart failure.
... Taurine decreases the effect of angiotensin II on cell Ca 2+ transport, protein synthesis, and angiotensin II signaling (Schaffer et al. 2000). Taurine may act centrally by interfering the action of glutamate. ...
Perinatal taurine depletion and high sugar intake from weaning onward worsen cardiac damage and arterial pressure control after ischemia/reperfusion (IR) in adult male and female rats, which can be ameliorated by high taurine diets or inhibition of renin-angiotensin system. This study tests if taurine supplementation ameliorates cardiac damage and arterial pressure control in adult female rats via alterations of both cardiac and systemic renin-angiotensin system. Female Sprague-Dawley rats were fed normal rat chow and drank water alone (control, C) or water containing 3% beta-alanine (taurine depletion, TD) from conception to weaning, and female offspring were subjected to high sugar intake (normal rat chow and 5% glucose in water; CG and TDG) or the normal rat diet (CW and TDW). At 7 weeks of age, half of the rats in each group received 3% taurine in water (CW+T, CG+T, TDW+T, and TDG+T). One week later, rats were subjected to IR or Sham procedures followed by renal nerve recording, plasma and cardiac angiotensin II measurements. Cardiac angiotensin II levels significantly elevated in CG, TDW, and TDG. Further, plasma angiotensin II concentrations were significantly elevated only in the TDG, in consistent with a significant increase in renal nerve activity to juxtaglomerular cells, but not renal vessels and tubules. These abnormalities were ameliorated by short-term taurine supplementation. Thus, in adult female rats that are perinatally depleted of taurine followed by high sugar intake after weaning, taurine supplementation decreases the adverse effects of cardiac IR via inhibition of both cardiac and systemic renin-angiotensin system overactivity.
... The mechanism by which the combination of lz 1.62 6 0.4 6.29 6 1.5* 6.6 6 2* 4.53 6 2* 2.27 6 1.1** , *** LDL 0.56 6 0.14 6.53 6 0.8* 6.26 6 1* 4.71 6 0.9* 3.96 6 1.8* , ** , *** Hydroperoxides (nmol/Eq g CUOOH) Liver 299 6 150 260 6 10* 210 6 40 310 6 70 310 6 100 Kidney 33 6 20 290 6 40 320 6 50* 430 6 60* , ** , *** 370 6 70* Heart 190 6 80 160 6 50 240 6 100 320 6 70** 78 6 50*** , **** Notes: Abbreviations:C: Control; DHR: Diabetics-Hypertensive Rats; lz: lemon zest; sp: sardine proteins; IPGTT: Plasma glucose during intraperitoneal glucose tolerance test; TAS: Total antioxidant status; TBARS: Thiobarbituric acid reactive substances; HDL: High-density lipoproteins; LDL: Low-density lipoproteins; and Statistical analysis was performed using the Tukey honestly significant difference test; *p < 0.05 vs C; **p < 0.05 vs DHR; ***p < 0.05 vs DHR-lz; ****p < 0.05vs DHR-sp Lipid profile and redox status and sp lowers BP could be because of the action of taurine and flavonoids on angiotensin II. In fact, taurine may decrease BP by attenuation of angiotensin II signaling, which causes vasoconstriction and consequently increases BP (Schaffer et al., 2000), and polyphenols could prevent angiotensin-induced hypertension, and pathological changes including vascular remodeling and vascular fibrosis (Aviram and Dornfeld, 2001;Yao et al., 2012). Increased levels of serum glucose, serum creatinine, urea and uric acid are the markers of diabetic nephropathy (Idonije et al., 2011). ...
Purpose
This paper aims to study the effect of green lemon zest combined with sardine proteins in diabetic hypertensive rats (DHRs).
Design/methodology/approach
Male Wistar rats (n = 30) weighing 250 ± 10 g were divided into five groups. The first group consumed a diet containing 20 per cent casein (C). The other four groups are rendered diabetic by intraperitoneal injection of streptozotocin (40 mg/kg body weight), then hypertensive by subcutaneous implantation controlled time-release pellet containing ouabain (0.25 mg/pellet). One untreated group (DHR) consumed 20 per cent casein and the three other groups consumed the same diet supplemented with 2 per cent green lemon zest (DHR-lz), or with 20 per cent of sardine protein (group DHR-sp) or with the combination of both sardine proteins and green lemon zest (group DHR-sp + lz).
Findings
DHRs feeding on the combination of both sardine protein (sp) and lemon zest (lz) induced a significant decrease of diastolic blood pressure and heart rates values compared with DHR (p < 0.05). The HDLC values were increased by +55 per cent in DHR-sp + lz compared with DHR group. Moreover, plasma non-HDLC concentrations were decreased significantly compared to DHR, DHR-lz, DHR-sp and C groups. In DHR-sp + lzvs DHR group, TBARS values were decreased by −25 per cent in the liver. Moreover, kidney TBARS were significantly reduced by −66, −51, −65 and −67 per cent compared with C, DHR, DHR-lz and DHR-sp, respectively.
Originality/value
These results suggest that consumption of green lemon zest combined with sardine proteins can reduce blood pressure and tissue oxidative damage and, therefore, help to prevent cardiovascular complications in hypertensive diabetic patients.
... The elevation of multiple osmolytes in sperm from Gapdhs −/− and Pgk2 −/− mice could have functional consequences. For example, taurine regulates a wide range of physiological properties, often in association with changes in ion transport or protein phosphorylation [75]. It is also interesting to note that mice lacking choline dehydrogenase exhibit male infertility, with defects in sperm mitochondria, ATP levels, and motility [76]. ...
Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDHS) and phosphoglycerate kinase 2 (PGK2), two isozymes restricted to the male germline, catalyze successive steps in the glycolytic pathway in mammalian sperm. Although gene targeting of each isozyme demonstrated that glycolysis is required for normal sperm motility and male fertility, the phenotype of mice lacking GAPDHS is more severe than that of mice lacking PGK2. This study examined sperm function, signaling pathways and metabolism to investigate factors that contribute to the phenotypic differences between these knockout models. Sperm from the two knockouts exhibited comparable deficits in zona binding, in vitro fertilization with or without zona drilling, and capacitation-dependent tyrosine phosphorylation. In contrast, signaling and metabolic differences were apparent prior to capacitation. Phosphorylation of sperm protein phosphatase 1, which has been associated with the acquisition of motile capacity during epididymal maturation, was deficient only in GAPDHS-null sperm. Carnitine, choline, phosphocholine and taurine were elevated in sperm from both knockouts immediately after collection from the epididymis. However, only carnitine levels in PGK2-null sperm were significantly different from wild-type sperm, while all four metabolites were significantly higher in GAPDHS-null sperm. We confirmed that glycolysis is required for robust hyperactivation, but found that the motility of PGK2-null sperm improved to levels comparable to wild-type sperm with pyruvate as the sole metabolic substrate. This non-glycolysable substrate did not improve progressive motility in GAPDHS-null sperm. These results identify multiple signaling and metabolic defects that are likely contributors to male infertility and the absence of progressive sperm motility seen in mice lacking GAPDHS.
... The effects of AngII on VSMC include arteriole contraction, increase in arterial blood pressure, and VSMC proliferation. [3,4] Previously, sulfur dioxide (SO 2 ) was considered a toxic gas, but recently, it was found to be generated endogenously in vivo from sulfur-containing amino acids. [5] L-cysteine is first oxidized to L-cysteinesulfinate by cysteine dioxygenase. ...
Background: Clarifying the mechanisms underlying vascular smooth muscle cell (VSMC) proliferation is important for the prevention and treatment of vascular remodeling and the reverse of hyperplastic lesions. Previous research has shown that the gaseous signaling molecule sulfur dioxide (SO2) inhibits VSMC proliferation, but the mechanism for the inhibition of the angiotensin II (AngII)-induced VSMC proliferation by SO2has not been fully elucidated. This study was designed to investigate if SO2inhibited VSMC proliferation in mice with hypertension induced by AngII.
Methods: Thirty-six male C57 mice were randomly divided into control, AngII, and AngII + SO2groups. Mice in AngII group and AngII + SO2group received a capsule-type AngII pump implanted under the skin of the back at a slow-release dose of 1000 ng·kg−1·min−1. In addition, mice in AngII + SO2received intraperitoneal injections of SO2donor. Arterial blood pressure of tail artery was determined. The thickness of the aorta was measured by elastic fiber staining, and proliferating cell nuclear antigen (PCNA) and phosphorylated-extracellular signal-regulated kinase (P-ERK) were detected in aortic tissues. The concentration of SO2 in serum and aortic tissue homogenate supernatant was measured using high-performance liquid chromatography with fluorescence determination. In the in vitro study, VSMC of A7R5 cell lines was divided into six groups: control, AngII, AngII + SO2, PD98059 (an inhibitor of ERK phosphorylation), AngII + PD98059, and AngII + SO2 + PD98059. Expression of PCNA, ERK, and P-ERK was determined by Western blotting.
Results: In animal experiment, compared with the control group, AngII markedly increased blood pressure (P < 0.01) and thickened the aortic wall in mice (P < 0.05) with an increase in the expression of PCNA (P < 0.05). SO2, however, reduced the systemic hypertension and the wall thickness induced by AngII (P < 0.05). It inhibited the increased expression of PCNA and P-ERK induced by AngII (P < 0.05). In cell experiment, PD98059, an ERK phosphorylation inhibitor, blocked the inhibitory effect of SO2on VSMC proliferation (P < 0.05).
Conclusions: ERK signaling is involved in the mechanisms by which SO2inhibits VSMC proliferation in AngII-induced hypertensive mice via ERK signaling.
... These results are also sustained by ex vivo studies, in which taurine was shown to lower neointimal hyperplasia and proliferation of VSMCs in rats suffering an iatrogenic carotid injury (46). Taurine demonstrated indirect effects on VSCMs proliferation by lowering angiotensin II vascular action and consecutive remodelling (15,47). Moreover, taurine lowered high plasma homocysteine levels induced by exogenous substances and antagonized the pro-oxidative effects of homocysteine on VSMCs (6,48). ...
Taurine, an ubiquitary amino acid in the organism, has important physiological functions like bile salt formation, neuronal excitability regulation, immunomodulation, electrolytes homeostasis preservation, osmoregulation, membrane stabilisation, apoptosis inhibition and cell protection. This review article is focusing on the complex vasoactive influence of the sulphur-amino acid and on the possibly involved mechanisms that may underline these effects. Acting on endothelial and smooth muscle cells in the vessels, it regulates blood pressure and delays atherogenesis process, having an increased therapeutic potential that needs to be further explored.
... 126,127 It has been reported that taurine reduced the cardiac hypertrophic effects of angiotensin II in adult rats, and taurine deficiency exacerbated the adverse actions of angiotensin II on the heart, blood vessels and kidneys. 128,129 Takahashi et al. examined the effect of taurine on angiotensin II-induced hypertrophy of cultured neonatal rat heart cells. They found that taurine suppressed angiotensin II-mediated stimulation in protein synthesis, attenuated immediate early response gene expression, and partially prevented the increase of intracellular free Ca 2+ mediated by angiotensin II. ...
Metabolic syndrome, a cluster of risk factors for diabetes and cardiovascular disease, has become a very serious public health concern. A number of studies provide the evidence that taurine has the efficient action to metabolic syndrome, includes reducing triglycerides to prevent obesity, improving insulin resistance to regulate glucose metabolism, lowering cholesterol especially decreasing VLDL+LDL cholesterol and increasing HDL cholesterol to prevent diet-induced hypercholesterolemia, regulating renin-angiotensin-aldosterone system and kallikrein-kinin system etc. to reduce blood pressure. This review summarizes the data from in vitro, animal and limited human studies of beneficial effects of taurine to obesity, dyslipidaemia, diabetes mellitus and hypertension, and addresses the possible metabolic and molecular mechanisms of taurine in preventing metabolic syndrome.
... Similar results were reported by (Saad and Al-Rikabi 2002;Tabassum et al. 2007). The protective effect of Tau against CP-induced renal toxicity could be attributed to the osmoregulatory activity (natriuresis and diuresis) and the renoprotective effect of Tau, as well as its antioxidant activity by scavenging ROS, attenuating lipid peroxidation, and thus stabilizing biomembranes (Nandhini et al. 2005;Schaffer et al. 2000). ...
Cyclophosphamide (CP) is a cytotoxic alkylating agent used in the treatment of malignant diseases and autoimmune disorders. Its clinical use is limited to its marked cardiorenal toxicity. The present study aimed to investigate the possible protective role of taurine (Tau; 200 mg·kg(-1) per day, i.p.) on CP-induced cardiorenal toxicity. CP (200 mg·kg(-1)) was administered as a single intraperitoneal injection whereas; Tau was administered for 3 weeks on a daily basis. The results showed that CP produced an elevation in serum activities of creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, creatinine as well as blood urea nitrogen. CP also induced an elevation in the oxidative stress markers viz. elevation in the serum lipid peroxides level (measured as malondialdehyde; MDA) and reduction in reduced glutathione level and superoxide dismutase activity in both heart and renal tissue. On the other hand, administration of Tau attenuated the CP-evoked disturbances in the above mentioned parameters. In addition, CP exhibited electrocardiographic (ECG) changes, which were significantly reversed by Tau treatment. Finally, the histopathological examination emphasized the obtained results. In conclusion, Tau is suggested to be a potential candidate to ameliorate CP-induced cardiorenal toxicity that may be related to its antioxidant activity.
... However, its metabolism and physiological functions have eluded a complete understanding in spite of intensive research efforts over the last 30-40 years. There are several excellent reviews concerning the general physiological actions and metabolism of taurine (Jacobsen & Smith 1968;Hayes & Sturman 1981;Huxtable 1992;Schuller-Levis & Park 2006), as well as more specialized topics such as its role in development (Chesney 1988;Gaull 1989;Sturman 1993;Chesney et al. 1998), CVD (Wójcik et al. 2010;Yamori et al. 2010;Zulli 2010), hypertension (Schaffer et al. 2000;Militante & Lombardini 2002), diabetes (Franconi et al. 2006;Kim et al. 2007;Schaffer et al. 2009;de la Puerta et al. 2010), and the renal system (Chesney et al. 2010;Han & Chesney 2012). ...
The health benefits of a diet high in seafood cannot be fully explained by the omega-3 polyunsaturated fatty acids (n-3 PUFAs). Other nutrients, such as taurine (a component that is abundant in seafood) have been found to contribute to beneficial effects. In this chapter, the dietary need for taurine is discussed, the taurine content of marine and other foods is presented, and the link between taurine, seafood, and health-promoting effects is outlined.
... For instance, taurine as well as the other organic osmolytes, promote proper protein folding and membrane trafficking of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein (delta508 CFTR) which fails to move out of the ER and into the plasma membrane without an organic osmolyte [20]. In addition, taurine modulates calcium transport [21], suppresses the generation of reactive oxygen species [22] and inhibits cellular apoptosis [23]. All of these actions are thought to contribute to the maintenance of cellular homeostasis. ...
Taurine (2-aminoethanesulfonic acid) is found in milimolar concentrations in mammalian tissues. One of its main functions is osmoregulation; however, it also exhibits cytoprotective activity by diminishing injury caused by stress and disease. Taurine depletion is associated with several defects, many of which are found in the aging animal, suggesting that taurine might exert anti-aging actions. Therefore, in the present study, we examined the hypothesis that taurine depletion accelerates aging by reducing longevity and accelerating aging-associated tissue damage. Tissue taurine depletion in taurine transporter knockout (TauTKO) mouse was found to shorten lifespan and accelerate skeletal muscle histological and functional defects, including an increase in central nuclei containing myotubes, a reduction in mitochondrial complex 1 activity and an induction in an aging biomarker, Cyclin-dependent kinase 4 inhibitor A (p16INK4a). Tissue taurine depletion also enhances unfolded protein response (UPR), which may be associated with an improvement in protein folding by taurine. Our data reveal that tissue taurine depletion affects longevity and cellular senescence; an effect possibly linked to a disturbance in protein folding.
... Blocking the actions of angiotensin II have been shown to suppress the development of atherosclerosis (Rosenson 2003). Taurine has been shown to antagonize the actions of angiotensin II (Takahashi et al. 1997;Schaffer et al. 2000), which may be partly responsible for the anti-inflammatory effects of taurine. ...
Taurine is abundantly present in most mammalian tissues and plays a role in many important physiological functions. Atherosclerosis is the underlying mechanism of cardiovascular disease including myocardial infarctions, strokes and peripheral artery disease and remains a major cause of morbidity and mortality worldwide. Studies conducted in laboratory animal models using both genetic and dietary models of hyperlipidemia have demonstrated that taurine supplementation retards the initiation and progression of atherosclerosis. Epidemiological studies have also suggested that taurine exerts preventive effects on cardiovascular diseases. The present review focuses on the effects of taurine on the pathogenesis of atherosclerosis. In addition, the potential mechanisms by which taurine suppress the development of atherosclerosis will be discussed.
... After injection of taurine in ventricular cerebral cavity, Yoshioka et al. (2007) showed that the diminished blood pressure in hypertensive rats was through a decrease in cerebral monoamines. A modulation of the renin angiotensin system (Schaffer et al., 2000) and or vasodilator liberation (Kamata et al., 1996) by taurine are not excluded from this effect. In this context, Ristori and Verdetti (1991) have found a direct effect of taurine on vascular muscle, partially dependant of the endothelium and do not block the vasoconstrictor effect of noradrenalin. ...
Taurine, a sulfur-containing amino acid, has been reported to play an antihypertensive role but the mechanism underlying this activity is yet to be defined. In this study, we investigate the effect of taurine on blood pressure by oral administration in conscious spontaneously hypertensive rats (SHR). Total heart weight, left ventricular weight, lipid peroxidation as well as glutathione (GSH) and superoxide dismutase activities (SOD) were determined together with histopathological examination of heart tissue. Results indicate that four weeks of oral taurine administered significantly decreased the systolic blood pressure from 174.6 ± 6.4 to 140.08 ± 8.2 mm Hg (p < 0.05). This was associated with significant reduction of the left ventricular mass in cardiac tissues. Lipid peroxidation of the heart tissue was depressed, while SOD and GSH activities significantly increased in SHR under taurine treatment. Moreover, histological inspection of cardiac sections revealed a smaller cardiomyocytes diameter in taurine-treated animals when compared to controls. We conclude that taurine reduces blood pressure in SHR and decreases cardiac hypertrophy by impacting the antioxidant activity.
... An HP diet has been shown to be related to the abnormal metabolism of calcium and phosphate in kidney disease patients [20,21] . Human bodies preferentially maintain the homeostasis of the serum calcium concentrations; however, if the balance is skewed, hormones act to exchange calcium between blood and bone and control urinary calcium excretion. ...
Background/aim:
The purpose of the study was to investigate the effects of a high-protein (HP) diet on bone metabolism in rats with adriamycin (ADR)-induced nephrotic syndrome.
Methods:
Nephrotic syndrome was established by weekly injections of ADR (2 mg/kg, i.p.) for 6 weeks. After a final injection, we confirmed that nephrotic syndrome had developed. Then, the rats were divided into two groups for the dietary treatments, namely the HP diet (30% of calories from protein) and the low-protein (LP) diet (7% of calories from protein), and were fed an isocaloric diet for the following 5 weeks.
Results:
Urinary protein and phosphate excretion were significantly greater in the HP diet group than in the LP diet group (p < 0.05). Serum parathyroid hormone and osteocalcin levels were significantly higher and lower, respectively, in the HP diet group (p < 0.05). Femur weight, femur mass index and femur calcium contents were significantly lower in the HP diet group than in the LP diet group (p < 0.05). Bone mineral density was significantly lower in the HP diet group than in the LP diet group (p < 0.05); however, bone mineral content did not differ between the two groups.
Conclusion:
We confirmed that an HP diet negatively affects bone mineral metabolism and bone density in ADR-induced nephrotic syndrome rats.
Taurine supplementation is recommended during perinatal life to provide sufficient taurine for fetuses and newborns. Furthermore, perinatal taurine supplementation affects cardiovascular and metabolic functions in adult life. In adults, taurine supplementation is reported to improve exercise training. The present study explored the effects of perinatal taurine supplementation followed by dynamic exercise training on cardiovascular and metabolic functions in adult male rats. Pregnant Wistar rats were maintained on water containing or lacking 3% taurine from conception to weaning. After weaning, male offspring were fed normal rat chow and water throughout the study. At 4 weeks of age, the taurine-treated and taurine-untreated rats were subjected to either a swimming exercise protocol (10–30 min a day, 5 day a week) for 12 weeks (Ex and TEx) or remained sedentary (C and T). At 16 weeks of age, kidney weight, mean arterial pressure, baroreflex sensitivity, plasma leptin, plasma triglyceride, blood urea nitrogen, plasma creatinine, and SGOT were not significantly different among the four groups. Compared to the control, perinatal taurine supplementation alone did not significantly affect any of the measured cardiovascular and metabolic parameters. Exercise training significantly decreased bodyweight, heart rate, and visceral adipocyte size, irrespective of perinatal taurine supplementation, but increased SGPT and heart weight when compared to the control. However, the effect of exercise on SGPT, but not heart weight, was abolished by perinatal taurine supplementation. These data indicate that perinatal taurine supplementation not only preserves the beneficial effects of dynamic exercise training on cardiovascular and metabolic functions but also prevents exercise-induced organ damage in adult male rats.
Objectives
The adverse deleterious influences of Ipomoea carnea on brain tissue and Taurine's relative ability to prevent this neurotoxicity have been examined. Methods:We utilized sixty Wistar male rats weighing 1752 g. The rats were allotted into 4 groups of fifteen each: The control group got saline i.p. daily for eight weeks; the Ipomoea carnea extract (ICE) group received ICE (15 mg/kg b.w./day) orally for eight weeks. Taurine-treated rats, in which rats were administered Taurine (200 mg·kg−1, i.p./Day) for 2 months. Taurine+ ICE group in which rats were supplemented with (200 mg·kg−1, i.p. Taurine + ICE 15 mg/kg b.w./day orally) for 2 months.
Result
The findings indicated that Ipomoea persuaded an increase in lipid peroxidation markers as well as a disruption in antioxidant homeostasis, along with brain and serum cholinesterase(AChE) elevated levels, tumor necrosis factor (TNF), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). A considerable drop (P<0.05) in the brain superoxide dismutase (SOD), catalase (CAT), and GSH in Ipomoea carnea. SOD, CAT, and GSH levels were enhanced in the Taurine co-treated group but did not achieve control levels. Ipomoea Furthermore, Induced apoptosis in brain tissue by Ipomoea carnea reflected in pro-apoptotic Bax, P53, and caspase 3 overexpression., while taurine upregulated the anti-apoptotic Bcl2 in addition to Histopathologic, electron microscope, and immunohistological brain examination finding support our finding concerning the protective role of taurine.
Conclusion
Our study proved the protective role of taurine as a supplement could recover Ipomoea carnea -induced oxidative changes and brain damage.
Taurine is a non-protein amino acid that is expressed in the majority of animal tissues. With its unique sulfonic acid makeup, taurine influences cellular functions, including osmoregulation, antioxidation, ion movement modulation, and conjugation of bile acids. Taurine exerts anti-inflammatory effects that improve diabetes and has shown benefits to the cardiovascular system, possibly by inhibition of the renin angiotensin system. The beneficial effects of taurine are reviewed.
Taurine plays a pivotal role in regulating glucose and lipid metabolism, blood pressure homeostasis, and obesity largely due to its cytoprotective, antioxidant, and anti-inflammatory actions. Despite promising data from animal studies in this scenario, the efficacy of taurine supplementation in human studies has been inconsistent. The main objective of this meta-analysis was to appraise the effects of taurine supplementation on liver markers and, secondarily, to explore anthropometric measures as well. Pubmed, SCOPUS, Web of Science, and Google Scholar were searched from inception to April 2020. There were 12 eligible peer-reviewed studies meeting the inclusion criteria. Most studies were conducted in patients with liver or metabolic dysregulation (diabetes, hepatitis, fatty liver, obesity, cystic fibrosis, chronic alcoholism, and cardiac surgery). The taurine dosage varied from 0.5 to 6 g/d for 15 days to 6 months. Pooled effect sizes suggested a significant effect of taurine administration on systolic blood pressure (weighted mean difference (WMD): -4.67 mm Hg; 95%CI, -9.10 to -0.25), diastolic blood pressure (WMD: -2.90 mm Hg; 95%CI, -4.29 to -1.52), total cholesterol (WMD: -10.87 mg/dl; 95%CI, -16.96 to -4.79), and triglycerides (WMD: -13.05 mg/dl; 95%CI, -25.88 to -0.22); however, it had no effect on fasting blood glucose (WMD: 0.06 mg/dl), HDL-C (WMD: 0.90 mg/dl), LDL-C (WMD: -6.17 mg/dl), as well as on body mass index (WMD: -0.46 kg/m²) and body weight (WMD: -0.47 kg) as the anthropometric measures. These findings indicate that, in patients with liver dysregulation, taurine supplementation can lower blood pressure and improve the lipid profile by reducing total cholesterol and triglyceride levels.
Taurine (2-aminoethanesulfonic acid) is a sulfur-containing organic acid possessing several important effects, including antioxidant and anti-inflammatory ones. Exposure to ionizing radiation generates free radicals and reactive oxygen species (ROS) in irradiated cells, and free radical generation leads to oxidative stress. It is known that radiation nephropathy includes an inflammation-based process in which ROS and cytokines are responsible. Different doses of explored radiation can cause apoptosis, inflammation and a profound oxidative stress in kidneys. Oxidative stress is involved in renal injury after exposure to both ionizing radiation and inflammation. In this review, we describe the protective effect of taurine against several kidney diseases and the potential effects of taurine in the mitigation of radiation nephropathy. We also report that X-irradiation decreased the expression of taurine and TauT in the kidney. Taurine administration suppressed the decrease in the expression of taurine and TauT in the kidney after radiation exposure. Taurine might contribute to the mitigation of kidney injury induced by radiation.
Introduction: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Taurine, an essential amino acid, plays a critical role in cardiovascular function. The present study was accomplished to investigate the beneficial role of taurine on atherogenesis and atherothrombosis indexes in patients with MI.
Materials & Methods: In this semi-experimental study, 16 cases, 50 to 60 years old suffering from myocardial infarction were randomly classified into two experimental (taurine supplement) and placebo groups. The subjects of the experimental group took 3 supplement capsules containing 500 mg of taurine before the 3 daily meals. The placebo group took 3capsules containing starch, at the same time as the experimental members. Plasma blood sampling was carried out on the subjects at baseline level and after the modified Bruce protocol with and without taurine supplements or placebo in the same conditions.
Findings: There were no statistically significant differences in the general data, such as age, weight, BMI and Vo2max between the taurine supplement group and the control (P
Throughout the last decade, the use of energy drinks has been increasingly looked upon with caution as potentially dangerous due to their perceived strong concentration of caffeine aside from other substances such as taurine, guarana, and L-carnitine that are largely unknown to the general public. In addition, a large number of energy drink intoxications have been reported all over the world including cases of seizures and arrhythmias. In this paper, we focus on the effect of energy drinks on the cardiovascular system and whether the current ongoing call for the products’ sales and regulation of their contents should continue.
Cisplatin (CDDP) is one of the most effective chemotherapeutic agent used in the treatment of many kind of solid tumors. Its primary side effect is nephrotoxicity. The aim of this study to investigate the effects of taurine on cisplatin-induced acute nephrotoxicity. A single intraperitoneal injection of CDDP (15 mg/kg, or 25 mg/kg) deteriorated the kidney functions as reflected by histopathological changes. Histopathological changes were observed in all cisplatin groups. In the cisplatin group, oxidative stress was evident in the cisplatin group by observing an increase in 8-OHdG expression, an indicator of oxidative DNA damage. CDDP also resulted to an increase in CD68 expression in the renal tissues of CDDP groups. Taurine transporter (TauT) was down-regulated, and p53 was up-regulated in renal tissues as indicated by immunohistochemical analysis. Administration with taurine prior to a cisplatin injection was able to protect against deterioration of kidney function, to abrogate the decline in anti-oxidants and to suppress the increase in DNA damage. Moreover, taurine inhibited p53 activation and improved the pathological changes induced by cisplatin. This study demonstrates the protective effects of taurine in attenuating the expression of pro-inflammatory mediators and in improving antioxidant capacity in the kidney of cisplatin-injected rats. Thus, taurine could be a beneficial dietary supplement to attenuate cisplatin induced nephrotoxicity.
The heart consumes more energy than any other organ, pumping approximately 5 L of blood per minute at rest and up to 24 L/min during vigorous exercise. It needs about 6 kg of ATP every day, which is 20–30 times its own weight. The main contributors to ATP synthesis are fatty acids (70 %), through β-oxidation, and glucose (30–40 %), through aerobic glycolysis. Because of this dependence on oxidative energy production, increases of cardiac activity are dependent on instantaneous parallel increases of oxygen availability and ATP production [1].
Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin-induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin-mediated cardiac ER stress dependent apoptotic death and inflammation. Mice were simultaneously treated with taurine (150 mg kg(-1) body wt, i.p.) and cisplatin (10 mg kg(-1) body wt, i.p.) for a week. Cisplatin exposure significantly altered serum creatine kinase and troponin T levels. In addition, histological studies revealed disintegration in the normal radiation pattern of cardiac muscle fibers. However, taurine administration could abate such adverse effects of cisplatin. Taurine administration significantly mitigated the reactive oxygen species production, alleviated the overexpression of nuclear factor-κB (NF-κB), and inhibited the elevation of proinflammatoy cytokines, adhesion molecules, and chemokines. Cisplatin exposure resulted in the unfolded protein response (UPR)-regulated CCAAT/enhancer binding protein (CHOP) up-regulation, induction of GRP78: a marker of ER stress and eIF2α signaling. Increase in calpain-1 expression level, activation of caspase-12 and caspase-3, cleavage of the PARP protein as well as the inhibition of antiapoptotic protein Bcl-2 were reflected on cisplatin-triggered apoptosis. Taurine could, however, combat against such cisplatin induced cardiac-abnormalities. The above mentioned findings suggest that taurine plays a beneficial role in providing protection against cisplatin-induced cardiac damage by modulating inflammatory responses and ER stress. © 2016 BioFactors, 2016.
• The evidence to support high-dose individual amino-acid supplementation to produce 'pharmacological' effects is continuing to build • The concept of 'conditionally essentiality' has broadened with the growing awareness of increased requirements for individual amino acids in specific pathologies • arginine, the precursor to nitric oxide, has been shown to produce clinical benefits in a range of conditions where production of this mediator is compromised • carnitine is central to energy production derived from fatty acids and has marked therapeutic potential in conditions affecting heart, skeletal muscle and spermatozoa • Glutamine is the preferred fuel for a variety of immune and gastrointestinal cells and shows some potential in improving the health of both tissues • Taurine is attributed with a growing list of actions, implicating it as a therapeutic agent particularly in cardiovascular and diabetic presentations • Tyrosine has been extensively investigated and confirmed as a nutritional equivalent of the 'adaptogen'.
In this chapter, you will be provided an overview of some of the most frequently used sports nutrition and physique-augmenting dietary supplements. For quick reference, the supplements are presented in alphabetical order using their Common, or “street” Name. The information is further presented in a revised and abbreviated monograph format. Each monograph details the dietary supplement by, 1) COMMON NAME, 2) OTHER NAMES (including, if applicable, abbreviations, primary plant source, and commercially licensed trade name), 3) COMMON USES (as pertaining to sports nutrition and physique augmentation), 4) REVIEW (of the relevant clinical data), and 5) DOSE (as has either been recommended in the literature or could confidently be determined to be safe and elicit an efficacious response).
Foods and specific nutrients can affect drug levels, half-life, clinical efficacy and toxicity through increasing or decreasing gastrointestinal absorption, reduce or enhance drug metabolism or excretion. Some drugs affect vitamin stores or may cause mineral or trace element deficiencies. Available information about drug–nutrient interactions of those medicinal drugs that tend to be used in CKD patients is reviewed with a focus on mechanisms. Paragraphs on novel oral anticoagulants and rules for the administration of oral drugs through feeding tubes have been added. Interactions between drugs and nutrients or foods continue to be under-investigated and surprisingly little is known about interactions with nutrients of commonly used medications in general and even more so for renal disease-specific drugs.
2-Aminoalkanesulfonic acids have been synthesized by a three-component alkene/SO3·-DMF/acetonitrile reaction, followed by hydrolysis. Trifluoromethanesulfonic acid was added to the amino-sulfonation mixture to accelerate the reaction and prevent the competitive formation of by-products. The reported two-step procedure provided a concise and versatile approach to new analogues of the natural amino acid taurine.
Publisher Summary Taurine, a sulfur‐containing amino acid present in high concentrations in mammals, plays an important role in several essential biological processes. Taurine is not incorporated into protein and is the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. The ideal biomarker or biological measure should be reliable, reproducible, noninvasive, simple to perform, and inexpensive. Samples for biological measures should be easily obtained from physiological fluids such as blood or urine. Taurine levels in physiologic fluids have been useful for both diagnosing pathology and establishing a disease modifying therapy. In the specific case of taurine, it is important that patient information include nutritional supplementation as well as information on disease status and medications. Taurine has been measured in biological fluids due to the importance of this simple amino acid and its relative ease of determination. Taurine has been measured in animal models of disease as well as a variety of human conditions. However, it remains unclear how taurine should be used as a biomarker and in which situations this measurement would be a good prognostic or diagnostic indicator.
Taurine is a semiessential amino acid, and its deficiency is involved in retinal and cardiac degenerations. In recent years, it was found that diabetes mellitus (DM) is associated with taurine, and many in vivo experimental studies showed that taurine administration is able to reduce the alterations induced by DM in the retina, lens, and peripheral nerve, although its effects on diabetic kidney are dubious. Interestingly, long‐term taurine supplementation reduces the mortality rate in diabetic rats. The mechanisms by which taurine exerts beneficial effects in DM are discussed below. Recently, it has been suggested that taurine deficiency may alter the endocrine pancreas “fetal programming,” increasing the risk of insulin resistance in adult life. The bulk of experimental data suggests that taurine administration could be useful in the treatment of type 1 DM and in the prevention of insulin resistance.
Despite the prevalence of high blood pressure worldwide, this disease generally commands less social awareness than do coronary artery disease and stroke. In addition, because hypertensive patients exhibit few symptoms, they are less likely to seek and obtain treatment. Moreover, compliance with traditional pharmacologic therapy is reduced by unacceptable side effects. Accordingly, there has been a renewed interest in non-pharmacologic antihypertensive therapy. Dietary manipulations are attractive as non-pharmacologic therapy because they can be instituted before diagnosis and may prevent blood pressure elevation. The Dietary Approaches to Stop Hypertension (DASH) trial demonstrated conclusively that moderate dietary manipulation could be successful as nonpharmacologic hypertension treatment. For many years, the focus of dietary intervention has been on intake of electrolytes. Indeed, the Joint National Commission reports on treatment of hypertension only briefly mention dietary protein as a potential approach to modify high blood pressure1,2 citing insufficient research in this area. Since that time, accumulating evidence (albeit sometimes contradictory) has indicated that dietary protein can influence blood pressure. A traditional view, still espoused by some today, had been that consumption of animal protein increases, whereas vegetable protein decreases, blood pressure. 3 Nevertheless, there is
2-Aminoalkanesulfonic acids have been synthesized by a three-component alkene/SO3·DMF/acetonitrile reaction, followed by hydrolysis. Trifluoromethanesulfonic acid was added to the amino-sulfonation mixture to accelerate the reaction and prevent the competitive formation of by-products. The reported two-step procedure provided a concise and versatile approach to new analogues of the natural amino acid taurine. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
The effects of dietary proteins on plasma lipids, on the process of oxidation and on homocysteinemia, platelet aggregation, atherosclerosis, arterial hypertension and thrombosis have been investigated in animal models and in humans. Although sometimes conflicting, the results of epidemiological surveys and experimental studies, show that, in contrast to vegetable proteins, animal proteins might be well promote the development of atherosclerosis in subjects genetically predisposed to atherosclerosis, particularly in hypercholesterolemic subjects. Their eventual effects on healthy subjects have not been still proven. For the analysis of the results, several factors have to be taken into account: genetic, dietary environment and fats in particular, cholesterol, dietary fibers and isoflavones. The atherogenic, hypertensive and thrombotic effects depend on the amino acid composition of proteins, on the nature of the peptides released during digestion and of the extent of their immunologic effects. The mechanisms behind these pathogenic effects are complex and still under discussion also new investigations are necessary.
AUTEUR(S)
Gérard DEBRY
MOTS-CLÉS
protéines alimentaires, lipides plasmatiques, athérosclérose, hypertension artérielle, thrombose.
KEYWORDS
dietary proteins, plasma lipids, atherosclerosis, arterial hypertension, thrombosis.
LANGUE DE L'ARTICLE
Français
Taurine, a ubiquitous endogenous sulfur-containing amino acid, possesses numerous pharmacological and physiological actions, including antioxidant activity, modulation of calcium homeostasis and antiapoptotic effects. There is mounting evidence supporting the utility of taurine as a pharmacological agent against heart disease, including chronic heart failure (CHF). In the past decade, angiotensin II blockade and β-adrenergic inhibition have served as the mainstay in the treatment of CHF. Both groups of pharmaceutical agents decrease mortality and improve the quality of life, a testament to the critical role of the sympathetic nervous system and the renin--angiotensin system in the development of CHF. Taurine has also attracted attention because it has beneficial actions in CHF, in part by its demonstrated inhibition of the harmful actions of the neurohumoral factors. In this review, we summarize the beneficial actions of taurine in CHF, focusing on its antagonism of the catecholamines and angiotensin II.
Objective:
The current study considers changes of the postnatal brainstem cell number and angiotensin receptors by maternal protein restriction (LP) and LP taurine supplementation (LPT), and its impact on arterial hypertension development in adult life.
Methods and results:
The brain tissue studies were performed by immunoblotting, immunohistochemistry, and isotropic fractionator analysis. The current study shows that elevated blood pressure associated with decreased fractional urinary sodium excretion (FENa) in adult LP offspring was reverted by diet taurine supplementation. Also, that 12-day-old LP pups present a reduction of 21% of brainstem neuron counts, and, immunohistochemistry demonstrates a decreased expression of type 1 angiotensin II receptors (AT1R) in the entire medial solitary tract nuclei (nTS) of 16-week-old LP rats compared to age-matched NP and LPT offspring. Conversely, the immunostained type 2 AngII (AT2R) receptors in 16-week-old LP nTS were unchanged.
Conclusion:
The present investigation shows a decreased FENa that occurs despite unchanged creatinine clearance. It is plausible to hypothesize an association of decreased postnatal nTS cell number, AT1R/AT2R ratio and FENa with the higher blood pressure levels found in taurine-deficient progeny (LP) compared with age-matched NP and LPT offspring.
Data have been presented on the taurine content in various mammalian and fish tissues as well as on pathways of its formation,
turnover, and numerous functions. Based on comparison of the character of the taurine effects on various animal functions
as well as of the fact of the presence of taurine in the more ancient by origin potential objects of the mammalian and fish
nutrition, it is suggested that the taurine polyfunctionality has appeared at different stages of the biota.
Key wordstaurine-polyfunctionality-mammals-fish
This work reports the interpretation of the spectra from high-resolution 1H MR spectroscopy of extracts, muscle, and whole Atlantic salmon, the latter using a MR image localization technique. It was possible to identify single chemical components, such as hypoxanthine, amino acids, anserine, lactate and some fatty acids, in extracts, whole muscle and whole fish. These techniques may have practical applications for i) the selection of live specimens for breeding, ii) the classification of both live specimens and fillets according to their qualitative and quantitative content of lipids and small molecules, which is of relevance for the nutritional value of fish, and iii) authentication analyses of Atlantic salmon.
Although it is a well-known fact that hemodynamic load is a major determinant of cardiac muscle mass and its phenotype, little is known as to how mechanical load is converted into intracellular signals of gene regulation. To address this question, we characterized the stretch-induced adaptation of cultured neonatal cardiocytes grown on a stretchable substrate in a serum-free medium. Static stretch (20%) of the cells was applied without cell injury. Stretch caused hypertrophy in myocytes and hyperplasia in non-myocytes. Stretch caused an induction of immediate-early genes such as c-fos, c-jun, c-myc, JE, and Egr-1, but not Hsp70. Immunostaining showed that the stretch-induced Fos protein localized in the nucleus of both myocytes and non-myocytes. Nuclear extracts from stretched myocytes contained DNA binding activity to the AP-1 and Egr-1 consensus sequences. In myocytes, the induction of immediate-early genes was followed by expression of "fetal" genes such as skeletal alpha-actin, atrial natriuretic factor, and beta-myosin heavy chain. DNA transfection experiments showed that the "stretch-response element" of the c-fos gene promoter is present within 356 base pairs of the 5'-flanking region, whereas that of the atrial natriuretic factor and the beta-myosin heavy chain genes is probably located outside of 3412 and 628 base pairs of the 5'-flanking region, respectively. These results demonstrate that the phenotype of stretched cardiocytes in this in vitro model closely mimics that of hemodynamic load-induced hypertrophy in vivo. This model seems to be a suitable system with which to dissect the molecular mechanisms of load-induced hypertrophy of cardiac muscle.
Thousands of pet cats die each year with dilated cardiomyopathy, the cause of which is unknown. Although taurine is present
in millimolar concentrations in the myocardium of all mammals, taurine depletion has not previously been associated with a
decrease in myocardial function in any species. In this study, low plasma taurine concentrations associated with echocardiographic
evidence of myocardial failure were observed in 21 cats fed commercial cat foods and in 2 of 11 cats fed a purified diet containing
marginally low concentrations of taurine for 4 years. Oral supplementation of taurine resulted in increased plasma taurine
concentrations and was associated with normalization of left ventricular function in both groups of cats. Since myocardial
concentrations of taurine are directly related to plasma concentrations and low plasma concentrations were found to be associated
with myocardial failure in cats, a direct link between decreased taurine concentration in the myocardium and decreased myocardial
mechanical function is proposed.
One of the major functions of taurine in the heart is the modulation of calcium transport (21). Depending on the status of the myocardium, taurine is capable of either increasing or decreasing intracellular calcium levels (21). This complicated biphasic pattern has been difficult to resolve mechanistically. The only rational explanation for this phenomenon assumes that taurine exerts multiple effects on calcium transport, some which promote myocyte calcium accumulation while others enhance cellular calcium loss.
Taurine has been reported to induce a positive inotropy in heart muscle [1–3]. Taurine was also reported to exhibit beneficial effects in the treatment of congestive heart failure [4], and to have protective effects against calcium overload [5,6] and cardiomyopathy [7,8]. Recently, Sperelakis and colleagues reported that taurine also exerts a positive inotropic effect in the perfused embryonic (20-day-old) chick heart, without greatly affecting the slow Ca2+ action potentials accompanying the contractions. They suggested that the positive inotropic effect of taurine was not mediated through an increase in the slow inward Ca2+ current.
Amino acid (taurine) was tested in the treatment of congestive heart failure, using a double-blind randomized crossover placebo-controlled trial in a broad spectrum of 62 patients. Taurine or inactive placebo given per day was 6 g divided into 3 doses, for 4 weeks each. Fifty-eight patients completed the protocol. After 4 weeks of taurine administration, there was a highly significant improvement in dyspnea, palpitation, crackles, edema, cardiothoratic ratio on chest X-ray film, and New York Heart Association functional class. Comparison of the general efficacy of taurine with placebo indicates that taurine is significantly more effective than placebo (p < 0.05). These data suggest that taurine therapy is clinically beneficial in patients with congestive heart failure.
Partial depletion of the taurine content in the rat retina was accomplished for up to 22 weeks by introduction of 1.5% guanidinoethanesulfonate (GES) in the drinking water. Taurine levels decreased by 50% after 1 week of GES treatment and by 80% at 16 weeks. Replacement of GES by taurine to the GES-treated rats from week 16 to 22 returned their taurine content to the control value. Whereas addition of taurine (1.5%) to the drinking water of control rats from week 16 to 22 elevated the retinal taurine content to 118% of the control value, the administration of untreated water to GES-treated animals for the 16 to 22 week time period increased the retinal taurine content to only 76% of the control value.
The amplitude of the electroretinogram (ERG) b-wave was decreased by 60% after GES-treatment for 16 weeks and maintained this reduced level for up to 22 weeks. Administration of taurine in the drinking water from week 16 to 22 returned the b-wave amplitude to a range not statistically different from the control values whereas the administration of untreated water produced less improvement.
After 6 weeks of GES treatment when the retinal taurine content was reduced by 70% and the amplitude of the b-wave was reduced by 50% (extrapolated from Figure 1), phosphorylation of a specific protein with an approximate molecular weight of 20K was increased by 94%. The increased phosphorylation of the ~20K protein observed after GES treatment was reversed when the animals were treated with taurine (1 1/2%) in the drinking water for an additional 6 weeks. There was no change in the phosphorylation of the ~20K protein when animals were treated with taurine for 6 weeks. The data obtained support the theory that taurine may have a regulatory effect on retinal protein phosphorylation.
Angiotensin II modulates several aspects of cardiac function, including myocardial contractility, heart rate and myocyte growth. Most of these actions are intimately associated with alterations in calcium transport. Since taurine also modulates calcium transport, we examined possible interactions between taurine and angiotensin II at the level of the major cellular extruder of calcium, the Na–-Ca2+ exchanger. Over a concentration range of 0.5–25 mM, Turne served as an effective inhibitor of angiotensin II-mediated stimulation of the exchanger. An Arrhenius plot of Na+-Ca2+ exchange activity revealed that angiotensin II (2 nM) increased transporter activity by reducing the activation energy of the transport process. Taurine (25 mM) inhibited the angiotensin II effect by partially preventing the reduction in activation energy. However, neither agent significantly altered the transition temperature, ruling out a change in membrane fluidity or an alteration in the rate limiting step of the transporter as a cause of the observed effects. Since the Na+-Ca2+ exchanger plays an important role in the handling of [Ca2+]i by the myocardium, the effect of taurine on angiotensin II's modulation of contractile function was also examined. Hearts perfused with buffer containing angiotensin 11 experienced a slight positive isotropic effect in the absence of taurine but this was converted to a negative inotropic effect in the presence of taurine. The data suggest that Turine inhibits some, but not all of the actions of angiotensin II. The possibility that a phosphorylation event is the site of the angiotensin II-taurine interaction is discussed.
It was previously reported that the mitochondrial fraction of the rat heart contained a specific protein with a molecular weight of approximately 44kDa whose phosphorylation was inhibited by taurine (Lombardini,1994a). Isolation of the 44kDa phosphoprotein on a 1-dimensional polyacrylamide gel using traditional glycine buffers followed by re-electrophoresing the cut out proportion of the gel which corresponds to the 44kDa protein on a tricine-buffered gel resulted in sufficient pure protein for sequence analysis. The results indicate that the 44kDa phosphoprotein is pyruvate dehydrogenase.
It has been previously demonstrated that taurine inhibits the phosphorylation of an 20K apparent molecular weight protein present in the mitochondrial fraction of the rat retina (Lombardini, 1991). In the present studies, various analogues of taurine were tested for their inhibitory activity on the phosphorylation of this 20K protein. The most potent analogues were ()trans-2-aminocyclopentanesulfonic acid (TAPS) and 1,2,3,4-tetrahydroquinoline-8-sulfonic acid (THQS) which were approximately 21 and 7 times more potent than the parent compound, taurine. Median-effect plots were used to calculate the inhibitory median effect and combination index values for the combined effects of taurine and taurine analogues. From these studies, it was determined that the inhibitory taurine analogues were antagonistic to taurine when used in combination with taurine to inhibit the phosphorylation of the 20K apparent molecular weight protein. It was also concluded that: 1) the distance between the nitrogen and sulfur atoms in the taurine structure was important for inhibitory activity; 2) if the nitrogen atom is either within or attached to an unsaturated ring structure the inhibitory potency was significantly decreased, and 3) if both the sulfur and nitrogen atoms are present within the ring structure the analogue has no activity.
Mechanisms of amino acid efflux during volume regulation in hypoosmotically treated isolated rat hearts were studied by collecting the coronary artery perfusate and analysis by high pressure liquid chromatography. Hypoosmotic stress resulted in marked percentage increases in perfusate taurine, aspartate and glutamate levels, smaller increases in phosphoethanolamine, glycine and alanine and non-significant increases in serine and glutamine. Amino acid levels declined during reperfusion with isosmotic perfusate. The anion channel blocker 4-acetamido-4′-isothiocyanostilbene-2:2′-disulfonic acid (SITS, 500 μM) significantly reduced hypoosmotic release of taurine, aspartate, glutamate and glycine. Furosemide reduced hypoosmotically-evoked releases of taurine, glycine, alanine and phosphoethanolamine. The polyunsaturated amino acids, arachidonic and linoleic also reduced amino acid efflux. Phospholipase A2 inhibition with 7,7-dimethyleicosadienoic acid (DEDA, 2 μM) reduced osmotically-evoked releases of taurine, aspartate and glutamate. 4-Bromophenacyl bromide (1 μM) inhibited osmotically-evoked release of glutamate and glycine. Combined applications of SITS+DEDA markedly reduced osmotically evoked release of all eight amino acids. Glutamate and aspartate effluxes were not inhibited by the glutamate transport inhibitor dihydrokainic acid (1 mM). These results indicate that the hypoosmotic stress, by inducing cell swelling, can initiate an amino acid efflux as part of a regulatory volume decrease. An opening of anion-permeant channels and phospholipase activation appear to be involved in the regulatory volume decrease phenomenon.
Mechanical stress is a major cause of cardiac hypertrophy. Although the mechanisms by which mechanical load induces cardiac cellular hypertrophy have long been a subject of great interest for cardiologists, the lack of a good in vitro system has hampered the understanding of the biochemical mechanisms. For these past several years, however, an in vitro cardiocyte culture system has made it possible to examine the biochemical basis for the signal transduction of mechanical stress. Passive stretch of cardiomyocytes cultured on silicone membranes activates protein kinase cascades of phosphorylation and induces an increase in protein synthesis and the expression of both immediate early genes such as c-fos, c-myc, c-jun, Egr-1, and late response genes such as β-myosin heavy chain and skeletal α-actin. Although an important question regarding how mechanical stimulus is converted into biochemical signals remains unknown, the cultured cardiomyocyte is a good model to examine the signal transduction pathways of mechanical stress
Mechanical stress is a major cause for cardiac hypertrophy. Although the mechanisms by which mechanical load induces cardiomyocyte hypertrophy have long been a subject of great interest for cardiologists, the lack of a good in vitro system has hampered the understanding of the biochemical mechanisms. For these past several years, however, an in vitro neonatal cardiocyte culture system has made it possible to examine the biochemical basis for the signal transduction of mechanical stress. Passive stretch of cardiac myocytes cultured on silicone membranes activates phosphorylation cascades and induces the expression of specific genes as well as the increase in protein synthesis. Although an important question regarding how mechanical stimulus is converted into biochemical signals remains unanswered, cultured cardiac myocytes may be a good model to examine the signal transduction pathways of mechanical stress.
The renin–angiotensin system plays an important role in the hypertrophic responses in cardiac myocytes through the activation of signal transduction pathways and expression of oncogenes. In the present study, we examined mechanical stretch-induced activation of mitogen-activated protein kinases (MAP kinases) using cultured cardiac myocytes derived from neonatal angiotensinogen gene deficient mice (Agt−/−) and neonatal wild type mice (Agt+/+). Within 2 minutes of being added to cardiac myocytes, angiotensin II activated MAP kinases and the response was completely blocked by pretreatment of the cardiac myocytes with CV-11974, a selective antagonist of angiotensin II type 1 receptors. Interestingly, mechanical stretch resulted in significantly greater activation of MAP kinases inAgt−/− cardiac myocytes than inAgt+/+ cardiac myocytes. CV-11974 failed to suppress the stretch-induced activation of MAP kinases inAgt−/− cardiac myocytes while it inhibited the activation inAgt+/+ cardiac myocytes. BQ123, an endothelin type A receptor antagonist, had no effect on stretch-induced activation of MAP kinases in cardiac myocytes from either mouse strain. These results suggest that cardiac RAS is important for stretch-induced MAP kinase activation inAgt+/+ cardiac myocytes; however, angiotensin II is not indispensable for mechanical stretch-induced activation of MAP kinases inAgt−/− cardiac myocytes.
The effects of taurine on L-type and T-type Ca+ channels is isolated 3-days-old embryonic chick heart cells were examined at different intracellular Ca2+ concentrations ([Ca]i), using whole-cell voltage clamp techniques. Experiments were performed at room temperature (22°C) and at a holding potential of −40 mV. When [Ca]i was pCa 7, addition of taurine to the bath solution reduced the L-type Ca2+ current (ICa(L))at 0 mV by 56.3±2.8% (n=5, P < 0.01) at 10mM, and by 73.2±2.6% (n=5, P < 0.001) t ±3. At pCa 10, ICa(L)) was unaffected (%, n=5, P < 0.05) by mM taurine and was enhacde by 47.3±2.4% (n = 5, P<0.01) by 20 mM taurine. Control fast and slow time constants of inactivation at pCa 7 (at + 10 mV) were 5.8±2.8 ms and 28.8±1.8 ms (n = 4), respectively; neither constant was modified by taurine. At pCa 10, the control fast and slow time constants were 15.8±1.0 and 67.7±3.8 ms (n = 4); the fast time constant was not affected by 10–20 mM taurine but the slow time constant was slowed by 14.5±2.9% (n = 4, P<0.05) by 10mM taurine and by 66.2±2.8% (n = 4, P<0.001) by 20 mM taurine. The inactivation curve for ICa(L) was not modified by taurine. The voltage for half-maximum inactivation () at pCa 7 was −26.5±4.6 mV (n = 5) in control cardiomyocytes and −29.6±13.2 mV (n = 5) in cardiomyocytes treated with 20 mM taurine; at pCa 10, the was −27.7±5.2 mV (n = 6) in control cardiomyocytes and −24.4±6.4 mV (n = 6) in taurine-treated cardiomyocytes (20 mM). Intracellular application of taurine (20 mM) inhibited ICa(L) by 63.0±2.8% (n = 4, P<0.01), even at pCa 10. In some cells in which only the ICa(L) current was observed under control conditions, addition of taurine (20 mM) inhibited the ICa(L) current but caused a ICa(T) current to appear (at holding potential of −80 mV). These results suggest that taurine has complex actions and may regulate [Ca]i by modulating Ca2+ channels (dependent on [Ca]i).
1.Taurine has recently been known to protect against ischemia and heart failure. Taurine possesses plenty of actions on the ion channels and transports, but is very non-specific.2.Taurine may directly and indirectly help to regulate the [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via Na-Ca exchange and Na+-taurine cotransport.3.Taurine can prevent the Ca2+ ([Ca]o or [Ca]i)-induced cardiac functions.4.Therefore, it seems possible that taurine could exert the potent cardioprotective actions even under the condition of low [Ca]i level as well as under the Ca2+ overload condition.5.The electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells, and neurons from recent studies are summarized.
In the present study, we examined the effect of angiotensin II on Ca2+ efflux from freshly isolated adult rat cardiomyocytes. Angiotensin II stimulated the efflux of 45Ca2+ from the cells in a concentration-dependent manner, at least in pharmacological doses of 10(-8) M to 10(-5) M. The 45Ca2+ efflux was inhibited by the type 1 angiotensin II receptor antagonist losartan, but not by the type 2 antagonist PD 123319. Angiotensin II also induced an increase in cytosolic free calcium ([Ca2+]i) and inositol trisphosphate formation within the cardiomyocytes. Angiotensin II-induced 45Ca2+ efflux and the increase in [Ca2+]i were both inhibited by thapsigargin, a specific inhibitor of the sarcoplasmic reticulum Ca2+ pump. The 45Ca2+ efflux was not affected by removal of the extracellular Ca2+ but was dependent on the presence of extracellular Na+. In addition, angiotensin II caused 22Na+ influx into the cells. These results indicate that angiotensin II stimulates Na+-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on the plasma membrane type 1 angiotensin II receptors. Angiotensin II-induced increase in [Ca2+]i may cause an activation of Na+/Ca2+ exchange which finally results in the stimulation of 45Ca2+ efflux from the cells. Since it is reported that Na+/Ca2+ exchange is important in calcium homeostasis within the cells, angiotensin II may play some role in the reduction of intracellular Ca2+ from isolated adult rat cardiomyocytes.
Transcription of the proto-oncogene c-fos is stimulated rapidly and transiently by serum growth factors and mitogens. Critical for this response is the serum-response element which is bound in vivo in a ternary complex containing the transcription factors p67SRF and p62TCF (ref. 2). Disruption of the ternary complex correlates with impaired induction by serum and phorbol ester. Mitogen-activated protein (MAP) kinase is a serine/threonine kinase which is activated 1-5 minutes after treatment of cells with mitogens and growth factors that induce re-entry into the cell cycle, making MAP kinase a candidate for the transmission of proliferative signals. Here we show that p62TCF is phosphorylated by MAP kinase in vitro and that phosphorylation results in enhanced ternary complex formation. Serum-starved Swiss 3T3 cells treated with epidermal growth factor, which induces MAP kinase in these cells, are induced to express c-fos and yield p62TCF active in ternary complex formation. In contrast, treatment of Swiss 3T3 cells with insulin, which does not activate MAP kinase under these conditions, does not lead to enhanced ternary complex formation nor does it induce c-fos transcription. Our results link the expression of the human c-fos proto-oncogene to signal transduction pathways known to be activated before its own induction.
Recent interest in the role of taurine in the heart stems from the observation that cats fed a taurine deficient diet develop a cardiomyopathy1. This condition is reversible, as evidenced by the restoration of normal cardiac function upon dietary supplementation with taurine2. These studies have accelerated the search for a physiological function for taurine. Although several theories of taurine action have been proposed, none adequately accounts for all of the multiple properties and actions of taurine. Therefore, this review will address both the strengths and weaknesses of the present proposals, including the possibility that taurine may exhibit multiple physiological roles in the heart.
Myocardial taurine concentrations were measured in cats with cardiac disease and in healthy cats fed diets with various concentrations of taurine. Group 1 was composed of 26 cats with 3 categories of naturally developing cardiac disease: dilatative cardiomyopathy (group 1A), 10 cats; hypertrophic cardiomyopathy (group 1B), 9 cats; and volume overload (group 1C), 7 cats. These cats had been fed various commercial diets. Group 2 was composed of 40 healthy cats that had been fed diets varying in taurine concentration (0 to 1% taurine) for at least 2 years. Mean myocardial taurine concentrations did not differ significantly between group-1 cats with dilatative cardiomyopathy and those with hypertrophic cardiomyopathy or volume overload. Cats in group 1A had a mean myocardial taurine concentration 3 times higher than healthy cats fed a taurine-free diet (P less than 0.002). Mean myocardial taurine concentrations did not differ significantly between group-1A cats and healthy cats fed a diet containing 0.02% taurine; group-1A cats had significantly lower mean myocardial taurine concentrations than did healthy cats fed a synthetic diet containing 0.05 or 1.0% taurine (P less than 0.001). Acute oral administration of taurine in 5 group-1A cats appeared to increase mean myocardial taurine concentrations, compared with similar cats not given taurine during treatment for cardiac failure. In group-2 cats, mean myocardial taurine concentrations increased directly with percentage of dietary taurine.
It has been previously observed that taurine inhibits PKC-activated phosphorylation of specific proteins including a approximately 20k Mr protein in rat cortical synaptosomes. In the present study, the mechanism of the above effects of taurine were investigated. In an intrasynaptosomal cytosol fraction obtained by subcellular fractionation, taurine did not have inhibitory effects on protein phosphorylation. However, taurine did inhibit the phosphorylation of the approximately 20k Mr protein in a reconstituted preparation containing intrasynaptosomal cytosol and mitochondria. Experiments measuring calcium uptake demonstrated that taurine increased the accumulation of 45Ca2+ in the mitochondrial fraction in incubation systems both in the absence and presence of added ATP. In addition, taurine inhibited the accumulation of 32P-labeled phosphatidic acid in synaptosomes indicative of a reduction in the levels of diacylglycerol. These results suggest that taurine may inhibit specific protein phosphorylation both by reducing cytosolic calcium levels and by inhibiting the turnover of phosphoinositides. These effects of taurine on the signal transduction cascade involving PKC and phosphoinositide metabolism indicate a potential biological role for taurine in the nervous system.
Isovolumic left ventricular (LV) preparations were used to assess myocardial failure associated with dietary taurine deficiency in cats. Adult female cats (n = 12) were fed a purified diet devoid of taurine for 6-8 mo. Six of the cats received 1,000 mg of crystalline taurine orally once daily. The remaining six cats were not provided taurine replacement. Compared with control preparations, hearts isolated from taurine-deficient cats generated significantly lower values for developed LV systolic pressure (107 +/- 6 vs. 66 +/- 15 mmHg; P less than 0.05), maximal rate of LV pressure rise (+dP/dtmax; 1,103 +/- 38 vs. 718 +/- 172 mmHg/s; P less than 0.05), and fall (-dP/dtmax; 930 +/- 46 vs. 587 +/- 129 mmHg/s; P less than 0.05). LV function curves generated by hearts from taurine-deficient cats were shifted downward and to the right of control curves, demonstrating inotropic depression. In addition, end-diastolic pressure-volume (compliance) relationships in hearts from taurine-deficient cats were shifted downward and to the right of controls in the direction of increased chamber compliance or distensibility. Ten millimolar taurine significantly improved inotropic indexes only in hearts from taurine-deficient cats but failed to affect diastolic compliance. Myocardial contractile dysfunction and LV chamber dilatation in hearts from taurine-deficient cats verify a causal association between dietary deficiency of this amino acid and dilated cardiomyopathy in this species.
Both angiotensin II and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), significantly depressed developed pressure, oxygen consumption, and coronary flow in isolated perfused rat hearts and caused a decrease in diastolic and systolic [Ca2+]i and [Ca2+]i transients. PMA and angiotensin II did not change the levels of cAMP but moderately decreased PCr/Cr. The decrease in systolic [Ca2+]i and amplitude of [Ca2+]i transients caused by PMA and angiotensin II resulted in depressed cardiac function. Hearts perfused with PMA and angiotensin II had a decreased sensitivity to extracellular calcium. Depressed developed pressure and oxygen consumption in the PMA- and angiotensin II-treated hearts may have been due to a decrease in amplitude of effective [Ca2+]i transients, because the [Ca2+]i threshold for cross-bridge interaction was presumably higher than the diastolic [Ca2+]i in these hearts.
The effect of angiotensin II on cultured neonatal rat heart myocytes was studied by measuring changes in cell length, the magnitude and kinetics of the calcium current, and changes in cyclic adenosine 3',5'-monophosphate (cAMP) and phosphoinositide metabolism. Spontaneous beating frequency of multicellular networks was increased by angiotensin II with a maximal increase of 100% above control values at concentrations of 5 nM or greater. The half-maximal response occurred at 0.6 nM angiotensin II. Shortening amplitude, shortening velocity, and relaxation velocity decreased concomitantly with the increasing contractile rate. In voltage-clamped single myocytes, both steady-state and transient components of the calcium current were increased by the addition of angiotensin II. Angiotensin II had no effect on either control or isoproterenol-stimulated adenylate cyclase activity in myocyte membranes. Neither the basal levels nor the isoproterenol-stimulated cAMP accumulation in intact cells was affected by addition of hormone. In myocytes labeled with [3H]inositol, angiotensin II stimulated the formation of [3H]inositol phosphates. One minute after addition of 5 nM angiotensin II, inositol monophosphate and inositol bisphosphate levels were increased to 73% and 99%, respectively, above control values and remained elevated at 10 minutes. Inositol trisphosphate levels were not significantly different from control values at either time point. Nifedipine (10 microM) had no effect on angiotensin II-induced increases in [3H]inositol phosphates. We conclude that the increases in both spontaneous beating rate and calcium current in angiotensin II-stimulated cultured neonatal heart cells are not dependent on cAMP or inositol trisphosphate levels but may involve sustained phosphoinositide hydrolysis.
The anionic requirements and the stoichiometric relationships of Na+-taurine cotransport into rat renal brush-border membrane vesicles (BBMV) were evaluated. External Cl- (100 mM) or Br- (100 mM) gradients supported the full overshoot of Na+-taurine symport and yielded similar high-affinity transport systems for taurine uptake. No active uptake of taurine was evident in the presence of external (100 mM) NaF, NaI, Na gluconate, or Na p-aminohippurate (PAH). Na+:taurine stoichiometry was 2.18:1 in the presence of Cl- and 1.60:1 in the presence of Br-. When the external anion gluconate was employed, Na+-dependent taurine uptake was negligible over the whole range of Na+ concentrations examined. Cl-:taurine and Br-:taurine stoichiometries in the presence of external Na+ were 0.97:1 and 0.81:1, respectively. External furosemide (1 mM) or bumetanide (1 mM) did not change taurine accumulation and kinetic parameters. The anionic transport inhibitors 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (5 x 10(-4) M), N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (10(-3) M) and p-chloromercuribenzoate (5 x 10(-4) M) significantly decreased initial rate of taurine uptake by 48, 31, and 31%, respectively. These data suggest that Na+-taurine cotransport into rat renal BBMV is Cl- or Br- dependent and probably operates by means of 2 Na+:1 Cl- or Br-:1 taurine carrier complex. Na+-taurine symport across the rat renal brush-border membrane surface is not affected by diuretics that influence NaCl cotransport but is affected by selected anionic transport inhibitors. An intact anionic binding site may be needed for this translocation process.
Diuretic and natriuretic activities of atrial extracts from BIO 14.6 (cardiomyopathic) and F1B (normal) hamsters at 180 days of age were measured by rat bioassay. Both activities were lower in BIO 14.6 extracts. Because of the reported protective action of taurine in the cardiomyopathic hamster, we tested the effect of 0.1 M taurine drinking upon the activity of atrial extracts. Urine flow and Na+ excretion were increased in both BIO 14.6 and F1B; however, comparatively larger increases in BIO 14.6 taurine drinkers abolished strain differences that were observed in water drinkers. Taurine drinking BIO 14.6 hamsters exhibited an increased plasma sodium concentration. Drinking of 0.6% NaCl also produced an elevated plasma sodium concentration in BIO 14.6. Extracts from hamsters with increased salt intake had diuretic and natriuretic activities that were not different from those of water drinkers. These findings confirm that ANF activity is deficient in BIO 14.6 hamsters, and this suggests a role for taurine in its production, release, and/or activation.
The effects of taurine on ATP-dependent calcium ion uptake and protein phosphorylation of rat retinal membrane preparations were investigated. Taurine (20 mM) stimulates ATP-dependent calcium ion uptake by twofold in crude retinal homogenates. In contrast, it inhibits the phosphorylation of specific membrane proteins as shown by acrylamide gel electrophoresis and autoradiography. The close structural analogue of taurine, 2-aminoethylhydrogen sulfate, demonstrates similar effects in both systems, i.e., stimulation of ATP-dependent calcium ion uptake and inhibition of protein phosphorylation, whereas isethionic acid and guanidinoethanesulfonate have no effect on either system. A P1 subcellular fraction of the retinal membrane preparation that contains photoreceptor cell synaptosomes has a higher specific activity for the uptake of calcium ions. Phosphorylation of specific proteins in the P1 fraction is also inhibited by the addition of 20 mM taurine. Taurine has no effect on retinal ATPase activities or on phosphatase activity, thus suggesting that it directly affects a kinase system.
The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end diastolic pressure but produced significant increases in left ventricular dP/dtmax, cardiac output, and left ventricular systolic pressure in control hearts, indicating that intravascularly administered taurine substantially increased cardiac performance. In propranolol (1 mg.kg-1) treated rabbits taurine significantly improved left ventricular dP/dtmax and cardiac output, which were previously depressed by propranolol. Taurine had the same effect on diltiazem (1 mg.kg-1) treated rabbits. In rabbits with aortic regurgitation a bolus injection of taurine improved cardiac performance. Continuous infusion of taurine (100 mg.h-1) also produced a significant increase in left ventricular dP/dtmax. These results suggest that taurine has a unique action as an inotropic agent and that it may be useful in the treatment of patients with congestive heart failure.
To examine the effect of daily treatment with taurine on improving the status of congestive heart failure (CHF), we used rabbits with artificially induced aortic regurgitation. Ten rabbits were treated daily with taurine (100 mg/kg by mouth) and eight with guanidinoethyl sulfonate (GES) (100 mg/kg by mouth) immediately after induction of aortic regurgitation. The cumulative mortality rate at 8 weeks in the taurine-treated CHF group was 10% (1 of 10) compared with 53% (16 of 30) in the nontreated CHF group and 75% (6 of 8) in the GES-treated CHF group (p less than 0.05). Although cardiac function (max dP/dt) in CHF rabbits was significantly decreased (p less than 0.001), taurine-treated CHF rabbits maintained the same values as control rabbits. Taurine content of the left ventricular tissue of the CHF rabbits was significantly increased (p less than 0.01). Administration of taurine and GES to control rabbits for 8 weeks affected neither the hemodynamics nor the taurine content of the heart. It was concluded that taurine slowed the rapid progression of heart failure and consequently prolonged life expectancy.
In a double-blind, randomized, crossover, placebo-controlled study, we investigated the effects of adding taurine to the conventional treatment in 14 patients with congestive heart failure for a 4-week period. Compared with placebo, taurine significantly improved the New York Heart Association functional class (p less than 0.02), pulmonary crackles (p less than 0.02), and chest film abnormalities (p less than 0.01). A benefit of taurine over placebo was demonstrated when an overall treatment response for each patient was evaluated on the basis of clinical examination (p less than 0.05). No patient worsened during taurine administration, but four patients did during placebo. Pre-ejection period (corrected for heart rate) decreased from 148 +/- 14 ms before taurine treatment to 137 +/- 12 ms after taurine (p less than 0.001), and the quotient pre-ejection period/left ventricular ejection time decreased from 47 +/- 9 to 42 +/- 8% (p less than 0.001). Side effects did not occur in the patients during taurine. The results indicate that addition of taurine to conventional therapy is safe and effective for the treatment of patients with congestive heart failure.
The concentration of taurine in the left ventricle of the heart was doubled in patients who had died of chronic congestive heart failure compared to patients who had died of other causes and had no cardiac pathology. In the absence of congestive heart failure, a similar elevation in taurine level was seen in patients with high blood pressure compared to patients with lower blood pressures. The levels of taurine in heart failure were not affected by digitalis treatment. The concentration of taurine in the aorta was almost the same in patients who had died of congestive heart failure and patients who had died of other causes, suggesting that the increase in concentration of taurine might be specific to the heart.
Taurine (2-aminoethanesulfonic acid) is known to have a cardiotonic action. The present study was designed to see whether oral treatment with taurine could improve the status of congestive heart failure induced by aortic regurgitation. Nine rabbits were treated daily with taurine (100 mg/kg) after producing aortic regurgitation. Cumulative mortality at 8 weeks in the non-treated group was 52% compared with 11% in the taurine-treated group (p less than 0.05). Cardiac function (max dP/dt) was significantly decreased in rabbits with aortic regurgitation, whereas in taurine-treated rabbits, cardiac function was maintained the same as control. The present data suggest that taurine prevented the rapid progress of heart failure, and consequently prolonged the life expectancy.
Taurine is a beta-sulfonic amino acid that serves as a nutrient important for developing brain and retina and as an osmolyte in the medullary collecting duct. The activity of the taurine transport system is regulated by substrate supply and by the external osmolality; these two stimuli induce changes in taurine transport. Increased medium osmolality (500 mosmol) stimulates taurine uptake into MDCK cells but not LLC-PK1 cells. The enhanced taurine uptake that occurs in response to hyperosmolality is localized primarily to the basolateral surface of MDCK cells, whereas the adaptive response to medium taurine concentration is expressed on both the apical and the basolateral surfaces of both cell lines. The response of MDCK cells to medium osmolality requires protein synthesis and RNA transcription and is expressed in the presence of microtubular toxins. When cell monolayers were loaded with taurine by incubation in high-taurine medium before increasing medium osmolality, the expected increase in taurine uptake was blunted. Similarly, increased external beta-alanine (500 microM) also prevented the anticipated increase in taurine accumulation in response to hypertonicity; aminoisobutyric acid and betaine (500 microM) partially prevented the increase in taurine transport after hypertonicity, whereas L-alanine had no effect. The concentration of taurine or structurally similar analogs in the external medium might modify the response of taurine accumulation after exposure to hypertonic medium, in that taurine-replete cells behave differently than taurine-depleted cells. These studies indicate that there are at least tow distinct mechanisms involved in the regulation of taurine transport: external taurine concentration and medium osmolality, with taurine concentration seeming to be the predominant stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
It has been suggested that phosphorylation of a 40S ribosomal protein, S6, regulates protein synthesis. Two distinct families of S6 kinase have been identified, the rsk-encoded 85- to 92-kD S6 kinase (RSK) and the 70- or 85-kD S6 kinase (p70S6K). We have previously shown that hypertrophic stimuli, such as angiotensin II (Ang II), rapidly activate RSK in cardiac myocytes. However, RSK and p70S6K are regulated by distinct mechanisms, and p70S6K, but not RSK, is the physiological S6 kinase in vivo in other cell types. Using cultured neonatal rat ventricular myocytes, we examined whether Ang II activates p70S6K and investigated the effect of rapamycin, a potent yet indirect inhibitor of p70S6K, on the Ang II-induced hypertrophic response. Immunoblot analyses indicate that cardiac myocytes express the 70- and 85-kD forms of p70s6K. Ang II caused a rapid and sustained activation of p70S6K through the type I Ang II receptor. Rapamycin inhibited Ang II-induced activation of p70S6K in a dose-dependent manner, with an IC50 of 0.14 ng/mL (0.15 nmol/L). Rapamycin did not inhibit Ang II-induced activation of tyrosine kinase, mitogen-activated protein kinase, RSK, and protein kinase C. The effect of rapamycin is unlikely to be mediated by its effect on p34cdc2 and p33cdk2 because Ang II did not activate these cell cycle-dependent kinases in cardiac myocytes. In contrast, a dose-dependent inhibition of p70S6K by rapamycin is very closely correlated with its inhibition of the Ang II-induced increase in protein synthesis. Interestingly, rapamycin did not affect the Ang II-induced activation of specific gene expression, including the immediate-early gene c-fos and fetal type genes, such as atrial natriuretic factor and skeletal alpha-actin. Moreover, rapamycin did not suppress Ang II-induced phenotypic changes at the protein level, such as increased atrial natriuretic factor secretion, expression of beta-myosin heavy chain, and organization of actin into sarcomeric units. These results indicate that p70S6K is activated by Ang II and that a rapamycin-sensitive signaling mechanism, most likely p70S6K, plays an essential role in the Ang II-induced increase in overall protein synthesis but not in Ang II-induced specific phenotypic changes in cardiac myocytes.
There remain some controversies about the effect of angiotensin II on intracellular Ca2+ concentration ([Ca2+]i) in cardiac myocytes. The aim of this study was to investigate different roles of intracellular Ca2+ in the responses to angiotensin II between cardiac myocytes and nonmyocytes.
Primary cultures of neonatal rat cardiac myocytes and nonmyocytes were prepared. [Ca2+]i was measured with indo-1. Cellular growth was assayed by [3H]thymidine uptake, RNA content, [3H]phenylalanine incorporation and protein content. Induction of immediate-early gene was examined by Northern blot analysis.
In myocytes, angiotensin II decreased [Ca2+]i transients, induced c-fos mRNA, and accelerated hypertrophy. These effects were completely suppressed by AT1 receptor blockade or protein kinase C inhibition. After chelation of extracellular Ca2+, angiotensin II caused no change in [Ca2+]i or no induction of c-fos in myocytes. Phorbol 12-myristate 13-acetate also decreased [Ca2+]i transients, caused c-fos induction, and provoked hypertrophy in myocytes. In nonmyocytes, angiotensin II increased [Ca2+]i transiently, induced c-fos mRNA and hypertrophy. These effects of angiotensin II were not fully abolished by protein kinase C inhibition. Extracellular Ca2+ chelation did not completely inhibit the effects of angiotensin II on [Ca2+]i or c-fos induction in nonmyocytes. Phorbol 12-myristate 13-acetate did not affect [Ca2+]i or cellular growth in nonmyocytes but did cause c-fos induction.
These results suggest that angiotensin II induces cellular hypertrophy and immediate-early genes through the activation of protein kinase C in myocytes, although angiotensin II decreases [Ca2+]i transients via this signaling pathway. Induction by angiotensin II of hypertrophy and immediate-early genes in nonmyocytes may be in part mediated by a transient increase in [Ca2+]i which acts synergistically with protein kinase C activation.
We have previously shown that mechanical stress induces activation of protein kinases and increases in specific gene expression and protein synthesis in cardiac myocytes, all of which are similar to those evoked by humoral factors such as growth factors and hormones. Many lines of evidence have suggested that angiotensin II (Ang II) plays a vital role in cardiac hypertrophy, and it has been reported that secretion of Ang II from cultured cardiac myocytes was induced by mechanical stretch. To examine the role of Ang II in mechanical stress-induced cardiac hypertrophy, we stretched neonatal rat cardiac myocytes in the absence or presence of the Ang II receptor antagonists saralasin (an antagonist of both type 1 and type 2 receptors), CV-11974 (a type 1 receptor-specific antagonist), and PD123319 (a type 2 receptor-specific antagonist). Stretching cardiac myocytes by 20% using deformable silicone dishes rapidly increased the activities of mitogen-activated protein (MAP) kinase kinase activators and MAP kinases. Both saralasin and CV-11974 partially inhibited the stretch-induced increases in the activities of both kinases, whereas PD123319 showed no inhibitory effects. Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974. When the culture medium conditioned by stretching cardiocytes was transferred to nonstretched cardiac myocytes, the increase in MAP kinase activity was observed, and this increase was completely suppressed by saralasin or CV-11974. These results suggest that Ang II plays an important role in mechanical stress-induced cardiac hypertrophy and that there are also other (possibly nonsecretory) factors to induce hypertrophic responses.
The effects of angiotensin II (Ang II) (10(-9) M to 10(-7) M) on calcium releases were established in ventricular myocytes from normal and renal hypertensive adult rats. From each peak systolic indo-1 ratio (405 nm/480 nm), amplitude variation, duration (rise time and fall time), and frequency of spontaneous calcium releases were investigated on freshly isolated cardiomyocytes at rest or under electrical stimulation. The following changes were observed: (1) in spontaneous contracting myocytes, an increase in frequency of calcium transients at 10(-7) M in normal cells (+157%, P < 0.05) and at whatever angiotensin II concentration in hypertrophied cells (10(-9) M: +79% P < 0.05; 10(-8) M +82%, P < 0.01; 10(-7) M: +285%, P < 0.01) with a greater sensitivity of hypertrophied cells to Ang II (P < 0.05 at 10(-9) M, P < 0.01 at 10(-8) M). (2) In stimulated myocytes, a prolongation of the duration of calcium transients at 10(-7) M in normal cells (+68%, P < 0.01) and at 10(-9) M, 10(-8) M, 10(-7) M in hypertrophied cells: (+36%, P < 0.05; +39%, P < 0.01; +77%, P < 0.01) with a greater sensitivity of hypertrophied myocytes (P < 0.05 at 10(-9) M and 10(-8) M). An increase in duration may be explained by the occurrence of calcium releases during the fall time of calcium transients. Thus, both in normal and hypertrophied myocytes, Ang II induced the occurrence of calcium releases with increased sensitivity of hypertrophied cells to Ang II. Such calcium releases are known to be a possible cause of arrhythmias termed "triggered activity".
1. Angiotensin II increases myocardial contractility in several species, including the rabbit and man. However, it is controversial whether the predominant mechanism is an increase in free cytosolic [Ca2+]i or a change in myofilament Ca2+ sensitivity. To address this question, we infused angiotensin II in isolated perfused rabbit hearts loaded with the Ca2+ indicator indo-1 AM and measured changes in beat-to-beat surface transients of the Ca2+i-sen