Publications (12)32.22 Total impact
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Article: Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion.
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ABSTRACT: Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.Canadian Journal of Physiology and Pharmacology 06/2012; 90(7):851-62. · 1.95 Impact Factor -
Article: A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia-reperfusion.
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ABSTRACT: Vascular peroxidase 1 (VPO1) can utilize reactive oxygen species (ROS) generated from NADPH oxidase (NOX) to catalyze peroxidative reactions. This study was performed to identify a novel pathway of NOX/VPO1 in mediating the oxidative injury following myocardial ischemia reperfusion (IR). In a rat model of myocardial IR, the infarct size, serum creatine kinase (CK) activity, apoptosis, NOX activity, NOX2 and VPO1 expression were measured. In a cell (rat heart-derived H9c2 cells) model of hypoxia/reoxygenation (HR), the apoptosis, NOX activity, NOX2 and VPO1 expression, and H(2)O(2) and HOCl levels were examined. In vivo, IR caused 54.8 ± 1.7 % infarct size in myocardium accompanied by elevated activities of CK, caspase-3 and NOX, up-regulated VPO1 expression and high numbers of myocardial apoptotic cells; these effects were attenuated by pretreatment with the inhibitor of NOX. In vitro, inhibition of NOX or silencing of NOX2 or VPO1 expression significantly suppressed HR-induced cellular apoptosis concomitantly with decreased HOCl production. Inhibition of NOX or silencing of NOX2 led to a decrease in H(2)O(2) production accompanied by a decrease in VPO1 expression and HOCl production. However, silencing of VPO1 expression did not affect NOX2 expression and H(2)O(2) production. H(2)O(2)-induced VPO1 expression was partially reversed by JNK or p38 MAPK inhibitor. Our results demonstrate a novel pathway of NOX2/VPO1 in myocardium, where VPO1 coordinates with NOX2 and amplifies the role of NOX-derived ROS in oxidative injury following IR.Archiv für Kreislaufforschung 05/2012; 107(3):266. · 7.35 Impact Factor -
Article: Alpha lipoic acid protects heart against myocardial ischemia-reperfusion injury through a mechanism involving aldehyde dehydrogenase 2 activation.
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ABSTRACT: Recent studies demonstrate that alpha lipoic acid can prevent nitroglycerin tolerance by restoring aldehyde dehydrogenase 2 (ALDH2) activity and ALDH2-mediated detoxification of aldehydes is thought as an endogenous mechanism against ischemia-reperfusion injury. This study was performed to explore whether the cardioprotective effect of alpha lipoic acid was related to activation of ALDH2 and the underlying mechanisms. In a Langendorff model of ischemia-reperfusion in rats, cardiac function, activities of creatine kinase (CK) and ALDH2, contents of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. In a cell model of hypoxia-reoxygenation, the apoptosis, ALDH activity, reactive oxygen species level, 4-HNE and MDA contents were examined. In the isolated hearts, ischemia-reperfusion treatment led to cardiac dysfunction accompanied by an increase in 4-HNE and MDA contents. Pretreatment with lipoic acid significantly up-regulated myocardial ALDH2 activity concomitantly with an improvement of cardiac dysfunction and a decrease in 4-HNE and MDA contents, these effects were blocked by the inhibitor of ALDH2. Similarly, in the cultured cardiomyocytes, hypoxia-reoxygenation treatment induced apoptosis accompanied by an increase in the production of reactive oxygen species, 4-HNE and MDA. Administration of lipoic acid significantly up-regulated cellular ALDH2 activity concomitantly with a reduction in apoptosis, production of reactive oxygen species, 4-HNE and MDA, these effects were reversed in the presence of ALDH2 or PKCε inhibitors. Our results suggest that the cardioprotective effects of lipoic acid on ischemia-reperfusion injury are through a mechanism involving ALDH2 activation. The regulatory effect of lipoic acid on ALDH2 activity is dependent on PKCε signaling pathway.European journal of pharmacology 03/2012; 678(1-3):32-8. · 2.59 Impact Factor -
Article: Beneficial effects of capsiate on ethanol-induced mucosal injury in rats are related to stimulation of calcitonin gene-related Peptide release.
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ABSTRACT: Capsiate is a non-pungent analogue of capsaicin from CH-19 Sweet peppers. Capsaicin is reported to trigger calcitonin gene-related peptide (CGRP) release through activation of transient receptor potential vanilloid subfamily member 1 (TRPV1) and produces beneficial effects on gastric mucosa. This study aimed to investigate whether capsiate is able to produce beneficial effects on gastric mucosa and whether the protective effects of capsipate occur through a mechanism involving the activation of TRPV1 and CGRP release. A rat model of gastric mucosal injury was established by the oral administration of acidified ethanol. Gastric tissues were collected for analysis of the gastric ulcer index, cellular apoptosis, activities of caspase-3, catalase and superoxide dismutase (SOD), and levels of CGRP, TNF-α, and malondialdehyde (MDA). Our results show that the acute administration of ethanol significantly increased the gastric ulcer index concomitantly with an increase in cellular apoptosis, caspase-3 activity, and TNF-α and MDA levels, as well as a decrease in the activities of catalase and SOD. Pretreatment with 1 mg/kg capsiate attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by an increase in CGRP level, catalase, and SOD activities, and a decrease in caspase-3 activity, and TNF-α and MDA levels. The effects of capsiate were inhibited by capsazepine, an antagonist of TRPV1. These results suggest that capsiate is able to produce beneficial effects on ethanol-induced gastric mucosal injury. These effects are related to the stimulation of CGRP release through the activation of TRPV1.Planta Medica 09/2011; 78(1):24-30. · 2.15 Impact Factor -
Article: Vanillyl nonanoate protects rat gastric mucosa from ethanol-induced injury through a mechanism involving calcitonin gene-related peptide.
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ABSTRACT: Previous studies have demonstrated that capsaicin-sensitive sensory nerves are involved in the protection of gastric mucosa against damage by various stimuli and calcitoin gene-related peptide (CGRP) is a potential mediator in this process. This study was performed to explore the effect of vanillyl nonanoate, a capsaicin analog, on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. A rat model of gastric mucosal injury was induced by oral administration of acidified ethanol and gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, the activities of caspase-3, catalase and superoxide dismutase (SOD), levels of CGRP, TNF-α and malondialdehyde (MDA). The results showed that acute administration of ethanol significantly increased gastric ulcer index concomitantly with increased cellular apoptosis, caspase-3 activity, TNF-α and MDA levels as well as decreased activities of catalase and SOD. Pretreatment with 1mg/kg vanillyl nonanoate significantly attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by increase of CGRP expression, and SOD activity and decrease of caspase-3 activity, TNF-α and MDA levels. The effects of vanillyl nonanoate were inhibited by capsazepine, an antagonist of capsaicin receptor. Our results suggested that vanillyl nonanoate was able to protect the gastric mucosa against ethanol-induced gastric mucosal injury. The underlying mechanism is related to stimulation of CGRP release and subsequent suppression of ethanol-induced inflammatory reaction, cellular apoptosis and oxidative stress.European journal of pharmacology 05/2011; 666(1-3):211-7. · 2.59 Impact Factor -
Article: Reversal of isoprenaline-induced cardiac remodeling by rutaecarpine via stimulation of calcitonin gene-related peptide production.
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ABSTRACT: Dysfunction of capsaicin-sensitive sensory nerves is involved in cardiac remodeling, and rutaecarpine has been shown to exert a beneficial effect on cardiac function through activating the sensory nerves. This study was conducted to explore the potential inhibitory effect of rutaecarpine on cardiac remodeling and the underlying mechanisms. A rat cardiac remodeling model was established by injection of isoprenaline (5 mg/kg per day, s.c.) for 10 days. Rutaecarpine (10 or 40 mg/kg, i.g.) was coadministrated with isoprenaline to evaluate the effect of rutaecarpine on cardiac remodeling. After echocardiographic analysis was performed, blood samples were collected to quantify calcitonin gene-related peptide (CGRP), dorsal root ganglia were isolated for examining CGRP mRNA expression, and the hearts were weighed and saved for evaluating the parameters related to apoptosis and hypertrophy. Isoprenaline significantly increased the ratio of left ventricle weight to body weight, the cross-sectional area of cardiomyocytes, cardiac apoptosis, and collagen deposition concomitantly with decreased CGRP production, which were reversed by rutaecarpine treatment. The beneficial effects of rutaecarpine were attenuated by pretreatment with capsaicin, which selectively depleted CGRP. These results suggest that rutaecarpine was able to reverse isoprenaline-induced cardiac remodeling through stimulating CGRP production.Canadian Journal of Physiology and Pharmacology 10/2010; 88(10):949-59. · 1.95 Impact Factor -
Article: Protective effect of phloroglucinol against myocardial ischaemia-reperfusion injury is related to inhibition of myeloperoxidase activity and inflammatory cell infiltration.
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ABSTRACT: 1. It has been shown that phloroglucinol has anti-inflammatory and anti-oxidant properties. Both inflammatory cell infiltration and myeloperoxidase (MPO) activation play an important role in myocardial reperfusion injury. The aim of the present study was to explore the effect of phloroglucinol on myocardial reperfusion injury and the mechanisms involved. 2. Anaesthetized rats were pretreated with phloroglucinol (15 or 30 mg/kg, i.g.) or vehicle (5 mmol/L carboxymethyl cellulose sodium) 30 min prior to experimentation. The left main coronary artery was subjected to 1 h occlusion followed by 3 h reperfusion. Infarct size, the release of creatine kinase (CK), inflammatory cell infiltration, MPO activity and protein content, catalase in the blood and myocardium, and myocardial apoptosis were measured. 3. Following myocardial ischaemia and reperfusion in vehicle-treated rats, infarct size was 43.5 ± 3.7% (relative to the area at risk). Accompanying detrimental changes included elevated CK, enhanced inflammatory cell infiltration, high numbers of myocardial apoptotic cells, elevated caspase 3 activity, increased MPO activity and content in the plasma and myocardium and reduced catalase activity. These effects were attenuated by pretreatment with both doses of phloroglucinol (15 and 30 mg/kg, i.g.). 4. The results of the present study suggest that phloroglucinol protects the myocardium against ischaemia-reperfusion injury in rats and that its beneficial effects are related to inhibition of MPO activity and inflammatory cell infiltration.Clinical and Experimental Pharmacology and Physiology 10/2010; 38(1):27-33. · 1.85 Impact Factor -
Article: Phloroglucinol protects gastric mucosa against ethanol-induced injury through regulating myeloperoxidase and catalase activities.
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ABSTRACT: It has been shown that oxidative stress plays an important role in the pathogenesis of ethanol-induced acute gastric mucosal injury, and phloroglucinol, a smooth muscle relaxant, has been reported to possess anti-oxidative properties. In this study, we explored the effect of phloroglucinol on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. The rat model of gastric mucosal injury was induced by oral administration of acidified ethanol, and the gastric tissues were collected for analysis of gastric ulcer index (UI), cellular apoptosis, anti-O(2) ˙ or OH˙ formation activity, malondialdehyde (MDA) content, and the activities of myeloperoxidase (MPO), catalase and glutathione peroxidase. The results showed that acute administration of ethanol significantly increased gastric UI concomitantly with the increased cellular apoptosis, MDA contents, MPO activity as well as the decreased activities of catalase and anti-O(2) ˙ or OH˙ formation, which was reversed by pretreatment with phloroglucinol. Although ethanol treatment significantly decreased the activity of glutathione peroxidase, pretreatment with phloroglucinol did not significantly affect the activity of the same. The results suggest that phloroglucinol could protect the gastric mucosa against ethanol-induced injury, which is related to inhibiting the MPO activity and increasing the catalase activity in the gastric tissues.Fundamental and Clinical Pharmacology 09/2010; 25(4):462-8. · 1.80 Impact Factor -
Article: The role of the DDAH-ADMA pathway in the protective effect of resveratrol analog BTM-0512 on gastric mucosal injury.
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ABSTRACT: A recent study showed that resveratrol, a polyphenol found in many plant species, exerts dual effects on gastric mucosal injury. By using the model of ethanol-induced gastric mucosal injury in the present study, we explored the effect of trans-3,5,4'-trimethoxystilbene (BTM-0512), a novel analog of resveratrol, on gastric mucosal injury and the possible underlying mechanisms. Gastric mucosal injury in the rat was induced by oral administration of acidified ethanol. The gastric tissues were collected for determination of the gastric ulcer index, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) contents, the activity of dimethylarginine dimethylaminohydrolase (DDAH) and superoxide anion (O2(-)) or hydroxyl radical (OH*) formation. The results showed that acute administration of ethanol significantly increased the gastric ulcer index concomitantly with the decrease in DDAH activity and NO content as well as the increase in ADMA content, effects that were reversed by pretreatment with BTM-0512 (100 mg/kg) or L-arginine (300 mg/kg). Administration of BTM-0512 did not show a significant effect on O2(-) or OH. formation. The results suggest that BTM-0512 could protect the gastric mucosa against ethanol-induced injury, which is mainly related to an increase in DDAH activity and subsequent decrease in ADMA content.Canadian Journal of Physiology and Pharmacology 05/2010; 88(5):562-7. · 1.95 Impact Factor -
Article: Role of anandamide transporter in regulating calcitonin gene-related peptide production and blood pressure in hypertension.
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ABSTRACT: To explore the role of anandamide (AEA) transporter in regulating calcitonin gene-related peptide (CGRP) production and blood pressure. Plasma levels of AEA, CGRP, asymmetric dimethylarginine (ADMA) and nitric oxide in patients with essential hypertension, spontaneously hypertensive rats (SHRs) and 2 kidney 1 clip hypertensive rats and the CGRP mRNA expression in dorsal root ganglion of rats were measured. Peripheral blood lymphocytes were isolated to examine the AEA transporter activity, the role of AEA transporter in regulating CGRP mRNA expression or the effect of exogenous ADMA on AEA transporter activity. In both hypertensive patients and SHRs, the plasma level of AEA was elevated, but the AEA transporter activity was attenuated concomitantly with decreased CGRP production. Moreover, plasma ADMA level in SHRs was elevated accompanied by decreased nitric oxide level. By contrast, the plasma AEA level was elevated accompanied by increased CGRP production in 2 kidney 1 clip hypertensive rats, and there were no significant changes in plasma levels of ADMA, nitric oxide and the AEA transporter activity. In vitro, exogenous administration of AEA upregulated CGRP mRNA expression in lymphocytes, which was inhibited by AEA transporter blocker, AM404, and the AEA transporter activity was reduced by ADMA. Decreased plasma CGRP level in patients with essential hypertension or SHRs is likely due to the reduced AEA transporter activity, and the increased ADMA level may account for the reduced AEA transporter activity.Journal of hypertension 07/2009; 27(6):1224-32. · 4.02 Impact Factor -
Article: Role of anandamide transporter in regulating calcitonin gene-related peptide production and blood pressure in hypertension
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ABSTRACT: Objectives: To explore the role of anandamide (AEA) transporter in regulating calcitonin gene-related peptide (CGRP) production and blood pressure. Methods and results: Plasma levels of AEA, CGRP, asymmetric dimethylarginine (ADMA) and nitric oxide in patients with essential hypertension, spontaneously hypertensive rats (SHRs) and 2 kidney 1 clip hypertensive rats and the CGRP mRNA expression in dorsal root ganglion of rats were measured. Peripheral blood lymphocytes were isolated to examine the AEA transporter activity, the role of AEA transporter in regulating CGRP mRNA expression or the effect of exogenous ADMA on AEA transporter activity. In both hypertensive patients and SHRs, the plasma level of AEA was elevated, but the AEA transporter activity was attenuated concomitantly with decreased CGRP production. Moreover, plasma ADMA level in SHRs was elevated accompanied by decreased nitric oxide level. By contrast, the plasma AEA level was elevated accompanied by increased CGRP production in 2 kidney 1 clip hypertensive rats, and there were no significant changes in plasma levels of ADMA, nitric oxide and the AEA transporter activity. In vitro, exogenous administration of AEA upregulated CGRP mRNA expression in lymphocytes, which was inhibited by AEA transporter blocker, AM404, and the AEA transporter activity was reduced by ADMA. Conclusion: Decreased plasma CGRP level in patients with essential hypertension or SHRs is likely due to the reduced AEA transporter activity, and the increased ADMA level may account for the reduced AEA transporter activity.Journal of Hypertension 05/2009; 27(6):1224-1232. · 4.02 Impact Factor -
Article: Calcitonin gene-related peptide-mediated antihypertensive and anti-platelet effects by rutaecarpine in spontaneously hypertensive rats
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ABSTRACT: We have previously reported that Chinese traditional medicine rutaecarpine (Rut) produced a sustained hypotensive effect in phenol-induced and two-kidney, one-clip hypertensive rats. The aims of this study are to determine whether Rut could exert antihypertensive and anti-platelet effects in spontaneously hypertensive rats (SHR) and the underlying mechanisms. In vivo, SHR were given Rut and the blood pressure was monitored. Blood was collected for the measurements of calcitonin gene-related peptide (CGRP), tissue factor (TF) concentration and activity, and platelet aggregation, and the dorsal root ganglia were saved for examining CGRP expression. In vitro, the effects of Rut and CGRP on platelet aggregation were measured, and the effect of CGRP on platelet-derived TF release was also determined. Rut exerted a sustained hypotensive effect in SHR concomitantly with the increased synthesis and release of CGRP. The treatment of Rut also showed an inhibitory effect on platelet aggregation concomitantly with the decreased TF activity and TF antigen level in plasma. Study in vitro showed an inhibitory effect of Rut on platelet aggregation in the presence of thoracic aorta, which was abolished by capsazepine or CGRP(8–37), an antagonist of vanilloid receptor or CGRP receptor. Exogenous CGRP was able to inhibit both platelet aggregation and the release of platelet-derived TF, which were abolished by CGRP(8–37). The results suggest that Rut exerts both antihypertensive and anti-platelet effects through stimulating the synthesis and release of CGRP in SHR, and CGRP-mediated anti-platelet effect is related to inhibiting the release of platelet-derived TF.Peptides.
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Institutions
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2009–2012
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Central South University
- School of Pharmaceutical Sciences
Changsha, Hunan, China
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