Resveratrol attenuates high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK. (5th September 2015)

• Record Type: Journal Article
• Authors: Guo, Shuang; Yao, Qing; Ke, Zhiqiang; Chen, Hongguang; Wu, Jiliang; Liu, Chao
• Is Part Of: Molecular and cellular endocrinology. Volume 412(2015)
• Page Start: 85
• Page End: 94
• Publication Date: 2015-09-05
• Subjects: Resveratrol -- Apoptosis -- ROS -- AMPK -- Cardiomyocytes -- NADPH; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.05.034
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: Resveratrol prevents high glucose-induced apoptosis in primary cultured neonatal rat cardiomyocytes. Resveratrol inhibits NADPH-derived ROS production and maintains endogenous antioxidant defenses in cardiomyocytes. The protection of resveratrol on cardiomyocytes is possibly mediated by AMPK related signaling pathway. Abstract: Background: Diabetic cardiomyopathy (DCM) suggests a direct cellular insult to myocardium. Hyperglycemia-induced oxidative stress and apoptosis have been implicated in the pathogenesis of DCM. NADPH oxidase is a major source of reactive oxygen species (ROS) generation in cardiomyocytes. Resveratrol, a naturally occurring polyphenol, has shown beneficial effects on some cardiovascular complications associated with diabetes. Objectives: We aimed to examine the role of resveratrol on high glucose-induced NADPH oxidase-derived ROS production and cardiac apoptosis, together with modulation of protein signaling pathways in cardiomyocytes. Methods: Primary cultures of neonatal rat cardiomyocytes were exposed to 30 mmol/L high glucose with or without resveratrol. Cell viability, apoptosis, superoxide formation, NADPH oxidase activity and its subunits expression, antioxidant enzymes activities, as well as the potential regulatory molecules AMPK, Akt and GSK-3β were assessed in cardiac cells. Results: Elevated ROS production induced by 30 mmol/L high glucose was inhibited with the addition of resveratrol in primary cultured neonatal rat cardiomyocytes. Consistently, resveratrol markedly suppressed the increased activity of NADPH oxidase and Rac1, as well as the enhanced expression of p67 phox, p47 phox, and gp91 phox induced by high glucose. Lipid peroxidation, SOD, catalase, GSH-px activity and GSH content was reversed in the presence of resveratrol. Moreover, the expression of pro-apoptotic protein Bax was down regulated while anti-apoptotic protein Bcl-2 was up regulated. And cardiac cell injury and apoptosis were markedly rescued by resveratrol. In addition, resveratrol significantly increased phosphorylation of AMP-activated protein kinase (AMPK) at Thr172 in cardiomyocytes exposed to high glucose. Compound C, the pharmacologic inhibitor of AMPK, could mostly abrogate roles of resveratrol on cardiomyocytes in high glucose. In contrast, Akt and GSK-3β were little influenced by resveratrol. Conclusions: Our data demonstrated that resveratrol protected cardiomyocytes against high glucose-induced apoptosis through suppression NADPH oxidase-derived ROS generation and maintenance endogenous antioxidant defenses. And the protective effects of resveratrol are mostly mediated by AMPK related pathway.