DJ-1 preserving mitochondrial complex I activity plays a critical role in resveratrol–mediated cardioprotection against hypoxia/reoxygenation–induced oxidative stress - 04/02/18
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Abstract |
Resveratrol has been demonstrated to have cardioprotective effects by attenuating ischemia/reperfusion (I/R)–induced oxidative stress injury, but its in-depth molecular mechanisms against I/R–induced oxidative stress is not fully elaborated. DJ-1 plays a role in maintenance of mitochondrial complex I activity and is closely associated with oxidative stress. Therefore, this study sought to determine the contribution of DJ-1-mediated maintenance of mitochondrial complex I activity to the anti-oxidative stress effect of Resveratrol in the H9c2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The results showed that Resveratrol significantly attenuated the H/R–induced viability loss and lactate dehydrogenase leakage, accompanied by decreases in intracellular reactive oxygen species (ROS) and malondialdehyde contents and increases in the reduced glutathione/oxidized glutathione ratio. Furthermore, Resveratrol increased the expression and mitochondrial translocation of DJ-1 and promoted the direct binding of DJ-1 with complex I subunits ND1 and NDUFS4, which in turn improved mitochondrial complex I activity and inhibited mitochondria–derived ROS production after H/R. Intriguingly, the anti-oxidative stress effect of Resveratrol could be partially blocked by DJ-1 siRNA and Complex I inhibitor Rotenone, respectively. Conclusively, these results indicated that DJ-1 is necessary for Resveratrol-mediated cardioprotective effects against H/R-induced oxidative stress damage, at least in part, through preserving mitochondrial complex I activity, and subsequently decreasing mitochondrial ROS generation.
Le texte complet de cet article est disponible en PDF.Keywords : Resveratrol, Hypoxia/reoxygenation injury, Oxidative stress, DJ-1, Mitochondrial complex I, Cardioprotection
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Vol 98
P. 545-552 - février 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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