Iveta Herichova

Comenius University Bratislava · Department of Animal Physiology and Ethology

Unlabelled: Although more than 100 years passed from the renin-angiotensin system (RAS) discovery, new knowledge is still ceaselessly accruing in this field. The present review provides brief overview on the history of the RAS investigation, circulating and tissue RAS, and outlines the physiological functions of the RAS major active substance, ang...

Shift work was positively associated with higher incidence of metabolic syndrome, obesity, cardiovascular disease, sleep disturbances, decreased immune functions, and cancer. Observed disorders were manifested usually after longer time of shift work (more than 10 years). On the other hand, disturbed daily profile of melatonin and cortisol during sh...

miRNAs are small regulatory RNA molecules involved in posttranscriptional gene silencing. Their biosynthesis results in the formation of duplex consisting of a leading and a passenger strand of mature miRNA. The leading strand exhibits the main activity but recent findings indicate a certain role of the passenger strand as well. Deregulated levels...

Colorectal cancer represents a leading cause of cancer death. MicroRNAs (miRNAs) are small non-coding RNA molecules that have been extensively studied in tumours, since changes in their levels can reveal patient prognosis. Cancer progression is also influenced by the circadian system whose functioning is based on the rhythmic expression of clock ge...

Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miR...

Radiofrequency electromagnetic fields (RF-EMF) exert pleiotropic effects on biological processes including circadian rhythms. miR-34a is a small non-coding RNA whose expression is modulated by RF-EMF and has the capacity to regulate clock gene expression. However, interference between RF-EMF and miR-34a-mediated regulation of the circadian oscillat...

Study was focused on regulatory interactions between the circadian system and the renin-angiotensin system in control of microRNA (miRNA) biosynthesis. Responsiveness of the miRNA biosynthetic pathway, selected pre-miRNAs and clock genes to angiotensin II (AngII) infusion was analysed in the suprachiasmatic nuclei (SCN), liver, kidney and heart dur...

Covid-19 progression shows sex-dependent features. It is hypothesized that a better Covid-19 survival rate in females can be attributed to the presence of higher 17β-estradiol (E2) levels in women than in men. Virus SARS-CoV-2 is enabled to enter the cell with the use of angiotensin converting enzyme 2 (ACE2). The expression of several renin-angiot...

Angiotensin-converting enzyme 2 (ACE2) was identified as a molecule that mediates the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several membrane molecules of the host cell must cooperate in this process. While ACE2 serves in a membrane receptor-mediating interaction with the surface spike (S) glycoprotein of SA...

The current study is focused on mechanisms by which the peripheral circadian oscillator in the prefrontal cortex (PFC) participates in food reward‐induced activity. The experimental group of male Wistar rats was trained to receive a food reward with a low hedonic and caloric value. Afterwards, animals were exposed to a 5h phase advance. Experimenta...

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their memb...

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was...

The incidence of colorectal cancer (CRC) shows a sex-dependent difference in humans. The aim of this study was to analyze estrogen receptor beta mRNA (ERbeta) expression in patients with CRC with respect to their gender and clinicopathological features. Since cancer progression is accompanied by tumor vascularization, VEGF-A (vascular endothelial g...

Objective. Epidemiological studies confirm that hypertensive patients respond differently to renin-angiotensin system (RAS) inhibition depending on their gender. The aim of present work is to focus on sex-dependent differences in RAS regulation under conditions of increased salt intake. Method. To investigate RAS, we measured the expression of angi...

Recent evidence supports the important role of the circadian system in cancer progression in humans. The aim of the present study is to evaluate clock (cry1, cry2 and per2) and clock-controlled (vascular endothelial growth factor-a, early growth response protein 1 and estrogen receptor β) gene expression in colorectal cancer and adjacent tissue and...

Colorectal cancer (CRC) exhibits differences in its features depending on the location of the tumor. The role of the circadian system in the carcinogenesis is accepted and many studies report different clock gene expression in tumors compared to healthy tissue, although a little attention is given to the changes in clock genes in tumors arising fro...

The effects of food reward on circadian system function were investigated in the hypothalamic nuclei, prefrontal cortex and liver. Food rewards of small hedonic and caloric value were provided for 16 days 3 h after light phase onset to male Wistar rats. The daily pattern of locomotor activity was monitored. Gene expression profiling performed in th...

OBJECTIVES: The circadian system regulates expression of wide range of transcriptional factors. Among them egr1 was shown to be under circadian control executed via E-box. However, tissue specificity of E-box mediated control was not investigated until now. DESIGN: We focused on the efficiency of circadian regulation of egr1 at both sides of blood-...

Background: Renin-angiotensin system (RAS) and its main product Angiotensin II (AngII) are in the focus of the pharmacological industry mainly because of hypertension treatment. Up-regulated RAS is generally associated with cardiovascular diseases and consequent organs injuries. The classic inhibition of RAS is based on the blocking of the type 1 A...

Background: Renin-angiotensin system (RAS) and its main product Angiotensin II (AngII) is in the focus of the pharmacological industry mainly because of hypertension treatment. Up-regulated RAS is generally associated with cardiovascular diseases and consequent organ injury. Classic inhibition of RAS is based on blocking of AngII receptors type 1...

Disturbances in regular circadian oscillations can have negative effects on cardiovascular function, but epidemiological data are inconclusive and new data from animal experiments elucidating critical biological mechanisms are needed. To evaluate the consequences of chronic phase shifts of the light/dark (LD) cycle on hormonal and cardiovascular rh...

Micro RNAs (miRNAs) represent a newly discovered class of regulatory molecules in the human body. miRNA is a short double stranded RNA sequence interfering with mRNA, causing in most cases, inhibition of translation. Synthesis of miRNAs shows an increasing developmental pattern and postnatally miRNAs are synthesized in all cells possessing transcri...

Micro RNAs (miRNAs) are small regulatory molecules of increasing biologists’ interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miR...

Under physiological conditions the mammalian circadian system is synchronized to a cyclic environment. The central oscillator in the suprachiasmatic nuclei (SCN) responds predominantly to an external light (L) dark (D) cycle. Peripheral oscillators are more efficiently synchronized by metabolic cues. When the circadian system is exposed to opposing...

Objective: Endogenous daily rhythms in physiology are regulated by the circadian system consisting of the central and peripheral components. The renin-angiotensin system, involved predominantly in water balance and blood pressure control, exerts 24 h rhythmicity in many of its parameters. The present study is aimed to study possible interactions b...

Glucose is molecule usually studied in relation to metabolism. Except for this traditional view, it is known that under certain conditions glucose can serve as a signal molecule for the circadian system. The circadian system is entrained by relevant synchronizing cues that can be tissue-dependent. Central oscillator is synchronized mainly by light-...

Deregulated expression of clock gene per2 has previously been associated with progression of cancer. The aim of the present study was to identify genes related to per2 expression and involved in cell cycle control. Patients surgically treated for colorectal carcinoma with up-regulated and down-regulated per2 expression in cancer versus adjacent tis...

The circadian system allows organisms to remain synchronized with rhythmic environmental changes with a 24-h period. The molecular mechanism of circadian oscillations is based on the rhythmic expression of clock genes organized in feedback loops. Alterations in the circadian system contribute to the development of several pathological conditions in...

Endogenous daily rhythms are generated by the hierarchically organized circadian system predominantly synchronized by the external light (L): dark (D) cycle. During recent years several humoral signals have been found to influence the generation and manifestation of daily rhythm. Since most studies have been performed under in vitro conditions, the...

Generation of circadian oscillations is based on rhythmic expression of clock genes and subsequent post-transcriptional and post-translational modifications. In addition to the central circadian oscillator - the suprachiasmatic nucleus (SCN), peripheral oscillators have been demonstrated in many tissues, including the heart and blood vessels. Melat...

Experimental models of diabetes serve as an useful tool to acquire deeper insight into the processes taking place during diabetic state. Insulin dependent diabetes can be induced by administration of chemical compounds alloxan or streptozotocin. Both chemicals are able to enter β-cells via glucose transporter GLUT2 and then through several mechanis...

Under synchronized conditions daily rhythms run in precise phase relationships. Long lasting shift-work disturbs circadian rhythms and causes metabolism dysfunction. As a result of frequent shifts of the light (L):dark (D) cycle the circadian system has to adjust to a new regimen repeatedly, and organism can never achieve complete adjustment of all...

The development of circadian rhythmicity of melatonin biosynthesis in the pineal gland starts during embryonic period in birds while it is delayed to the postnatal life in mammals. Daily rhythms of melato-nin in isolated pinealocytes and in intact pineal glands under in vivo conditions were demonstrated during the last third of embryonic developmen...

Plasma melatonin concentrations in non-dipping patients show a blunted daily rhythm. Melatonin has a capacity to improve disturbances in biological rhythms. Hypertensive TGR(mRen2)27 (TGR) rats with an upregulated renin-angiotensin system and inverted blood pressure profile were used to elucidate whether melatonin is able to influence the control o...

The circadian system drives postnatally rhythmic processes in the peripheral tissues. To extend information about embryonic stages, ontogeny of the circadian oscillations in chicken (Gallus gallus) heart and liver was analyzed. Nineteen day old embryos and 4-day old chicks were synchronized to a light:dark cycle and then the effects of light pulses...

The renin-angiotensin system (RAS) is altered in diabetes. The aim of our study was to investigate whether streptozotocin-induced diabetes was associated with a change in angiotensin II receptors AT (1) and angiotensin-converting enzyme (ACE) mRNA expression in the pancreas in vivo. Rats were synchronized to a 12:12 light:dark cycle. Pancreas tissu...

Melatonin plays a role in blood pressure (BP) control. The aim of this study was to determine whether melatonin concentrations and melatonin receptor levels are altered in L-NAME-treated, NO-deficient hypertensive rats. Two groups of male adult Wistar rats were investigated: rats (n=36) treated with NO-synthase inhibitor L-NAME (40 mg kg(-1)) and a...

Hypertensive TGR(mRen2)27 (TGR) rats represent a strain with genetically upregulated renin-angiotensin-aldosterone system. Simultaneously with development of hypertension, a daily profile in blood pressure (BP) inverts and in mature TGR rats BP is higher during the lighttime (L) than the darktime (D). Physiological mechanisms of inverted BP rhythm...

The circadian system is involved in the control of cell proliferation and apoptosis. The aim of this study was to analyze expression of the human per2 gene in patients who underwent surgery for colorectal carcinoma. The study included 25 patients of both genders. Patients were exposed to light from 6:00 a.m. until 9:00 p.m. according to standard ho...

The chicken pineal gland possesses the capacity to generate circadian oscillations, is able to synchronize to external light:dark cycles and can generate an hormonal output--melatonin. We examined the light responses of the chicken pineal gland and its effects on melatonin and Per2, Bmal1 and E4bp4 expression in 19-day old embryos and hatchlings du...

Circadian system regulates rhythms with 24 h period including those occurring in the cardiovascular system. Inverted blood pressure profile was demonstrated in hypertensive TGR(mREN-2)27 (TGR) rats with upregulated renin-angiotensin system. To depict structures involved in the generation of the inverted pattern of blood pressure in TGR rats, we ana...

Exogenous melatonin was found to protect target organs under conditions of diabetes mellitus, however, concentrations of the hormone in peripheral tissues have not been determined. Therefore the aim of the present study was to measure the daily profile of melatonin levels in the pineal gland, plasma, pancreas, kidney, spleen, duodenum and colon of...

Hypertensive TGR(mREN-2)27 rats exerting inverted blood pressure (BP) profile were used to study clock gene expression in structures responsible for BP control. TGR and control Sprague Dawley male rats were synchronized to the light:dark cycle 12:12 with food and water ad libitum. Daily rhythm in per2, bmal1, clock and dbp expression in the suprach...

Stebelová K., M. Mach, I. Herichová, E. Ujházy, M. Zeman: Melatonin Concentration in Plasma, Pineal Gland and Duodenum of Pregnant Rats and their Fetuses after Melatonin and Phenytoin Administration. Acta Vet. Brno 2006, 75: 161-167. Melatonin (MEL) is involved in regulation of variety of physiological processes. Beside the pineal gland, the presen...

The circadian system is a flexible framework allowing a proper adjustment of physiological functions to the regularly changing environment. Pathways that are used to synchronize components of the circadian system have been shown to be susceptible to pathophysiological conditions. In our study, we investigated effects of streptozotocin (STZ)-induced...

Some patients with hypertension exhibit disturbed circadian organization in the cardiovascular system. Hormone melatonin can synchronize circadian rhythms and its repeated administration can improve synchronization of rhythmicity in blood pressure (BP). In our study we measured endogenous melatonin production in patients with essential hypertension...

The herbicide diquat (DIQ) is able to generate reactive oxygen species and possesses mutagenic activity. Protective effects of the pineal product melatonin (MEL) against oxidative damage have been demonstrated under both in vivo and in vitro conditions but exact mechanism and targets are not known. In the present study we evaluated possible protect...

Endogenous circadian rhythms govern cycles in rest-activity, food intake and metabolism, and profoundly affect performance of animals. Daily rhythms are mediated and imposed on the organism through the circadian system consisting from the hypothalamus, pineal gland and retina that contain multiple self-sustained circadian oscillators. The main sign...

In addition to a light-dark cycle, temperature cycles are also capable of synchronising the circadian rhythm of melatonin production in the chick embryo. Exposure of 19-day chick embryos to a low temperature of 4°C for 60 min during the dark-time increased a pineal melatonin content. By contrast, exposure of eggs to a high temperature of 41°C did n...

Objective: Several interleukins (ILs) including IL-1 beta and IL-6 are produced in the anterior pituitary (AP) where they probably participate in the local regulation of hormone production. Immune challenge brings about the dysregulation of immune-endocrine interaction and enhanced the expression of pituitary IL-1 beta and IL-6. Little is known ab...

We studied the effects of adjuvant arthritis (AA) on the endocrine circadian rhythms of plasma prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), testosterone, and melatonin and of pituitary PRL and GH mRNA in male Long Evans rats. Groups of control and AA rats (studied 23 days after AA induction)...

Development of a daily rhythmicity in transcription of a gene encoding a rate-limiting enzyme of melatonin biosynthesis, the arylalkylamine-N-acetyltransferase (AA-NAT) was studied by northern blot analysis in pineal glands of 16 and 19-day-old embryos and 1, 4, 8, 11, and 14-day-old chicks. In a parallel experiment, melatonin content in pineal gla...

Zeman, M., J. Buyse, J., I. Herichová, E. Decuypere: Melatonin Decreases Heat Production in Female Broiler Chickens. Acta Vet. Brno 2001, 70: 15-18. The principal hormone of the pineal gland, melatonin, is involved in the control of circadian rhythms in birds. Moreover, several studies link melatonin with modulation of metabolism and growth in chic...

In the submitted paper experimental results are interpreted comparing the administration of two fundamental anti-glaucomatous drugs into the conjunctival sac of healthy rabbits of the Chinchilla strain. The authors administered 2% pilocarpine and 0.25% Timoptol (Timololi maleas, Léciva) alone, as combined consecutive administration and concurrent a...

The distinct melatonin rhythm with higher concentrations during the darktime was found in plasma of both control patients and patients with colorectal carcinoma. Moderate surgery did not induce any changes in plasma melatonin levels, but a pronounced increase in both the day- and nighttime melatonin concentrations was found after surgical treatment...

The pineal hormone melatonin controls reproduction of photoperiodic mammals and is an integral part of the circadian organization in birds. Recent findings indicate an involvement of this hormone also in more basic physiological processes, including growth, development, and aging. Melatonin may modulate growth in poultry through interaction with tr...

Besides the well known role of melatonin in regulation of daily rhythmicity in birds and seasonal cycles in photoperiodic mammals, pleiotropic effects of melatonin mediated by interactions with endocrine and immune systems or through specific receptors in peripheral tissues, were suggested. In the present study we measured melatonin levels in the p...

In contrast to the situation in mammals, in which circadian melatonin production by the pineal gland does not begin until some time after birth, the development of pineal gland rhythmicity is an embryonic event in the precocial domestic fowl. A distinct melatonin rhythm was found in 19-d-old chick embryos maintained under light:dark (LD) 16:8. No s...

Melatonin is involved in the control of a wide range of physiological processes, including the modulation of gastrointestinal functions. Presence of high levels of this indoleamine in the gastrointestinal tract (GIT) was proved, however, factors influencing its concentrations in this system are still to be elucidated. Therefore we tested effects of...