Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac muscle cells

Abstract

Resveratrol, one of polyphenols derived from red wine, has been shown to protect against cell death, possibly through the association with several signaling pathways. Currently numerous studies indicate that cardiovascular diseases are linked to the release of intracellular reactive oxygen species (ROS) often generated in states such as ischemia/reperfusion injury. In the present study, we investigated whether resveratrol has the capability to control intracellular survival signaling cascades involving AMP-activated kinase (AMPK) in the inhibitory process of cardiac injury. We hypothesized that resveratrol may exert a protective effect on damage to heart muscle through modulating of the AMPK signaling pathway. We mimicked ischemic conditions by inducing cell death with H 2 O 2 in H9c2 muscle cells. In this experiment, resveratrol induced strong activation of AMPK and inhibited the occurrence of cell death caused by treatment with H 2 O 2 . Under the same conditions, inhibition of AMPK using dominant negative AMPK constructs dramatically abolished the effect of resveratrol on cell survival in H 2 O 2 -treated cardiac muscle cells. These results indicate that resveratrol-induced cell survival is mediated by AMPK in H9c2 cells and may exert a novel therapeutic effect on oxidative stress induced in cardiac disorders.

Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure

“…Previous in vitro studies suggested that resveratrol-induced cell survival was mediated by AMPK in H9c2 cells, and resveratrol-induced glucose uptake was observed in vitro in H9c2 cardiac myoblast cells through the AMPK pathway (Hwang et al, 2008;Penumathsa et al, 2008). In our study, we also found that resveratrol, through SIRT1 activation, could increase AMPK expression in heart failure rats, and that the expression of AMPK was decreased in SIRT1(+/-) mice.…”

Resveratrol Protects Human Endothelium from H2O2-Induced Oxidative Stress and Senescence via SirT1 Activation

“…Recently, Robb et al demonstrated that RV can markedly induce mitochondrial MnSOD expression and activity in MRC-5 cells, as well as in mouse brain tissues 42) . Moreover, RV has been shown to protect against ROS-induced cell death by activating AMP-activated kinase in cardiac muscle cells 43) . Our findings demonstrated that, even with RV treatment, knockdown of SirT1 in HUVECs increased ROS production and further promoted the development of oxidative stress-induced senescence in human endothelial cells (Fig.…”

Overexpression of Aldose Reductase Render Mouse Hepatocytes More Sensitive to Acetaminophen Induced Oxidative Stress and Cell Death

“…Importantly, the present study showed over-expression of aldose reductase deactivated AMPK by decreasing its phosphorylation, therefore, we suggest that might suppressing activity of AMPK is the mechanism of aldose reductase induced ROS production and subsequence apoptosis and cell death. AMPK, an important energy sensor in cells, also plays an important role in cell survival/ death by regulating H 2 O 2 , previous studies demonstrated that activation of AMPK significantly reduced hydrogen peroxide induced necrosis and cell death in mouse primary culture hepatocyte and H9c2 cells respectively, and inhibition of AMPK promote hydrogen peroxide induced necrosis and cell death [23,24]. Moreover, the levels of ROS significantly increased in AMPK deficiency mice [25].…”