Resveratrol Inhibits Zinc Deficiency-Induced Mitophagy and Exerts Cardioprotective Effects

Resveratrol (Res) has cardioprotective, anti-inflammatory, anti-aging and antioxidant effects; however, its mechanism remains unclear. Here we explored the protective effects of resveratrol on cardiomyocytes, focusing on the role of Zn 2+ and mitophagy. Using the MTT/LDH assay, we found that addition of a zinc chelator TPEN for 4h induced mitophagy and significantly reduced cell viability, increased cytotoxicity and apoptosis in H9c2, while Res significantly inhibited these effects of TPEN. Similarly, Res inhibited TPEN-induced expression of mitophagy-associated proteins P62, LC3, PINK1, Parkin and TOM20. The mitophagy inhibitor 3-MA blocked the function of Res. At the same time, we found that Mfn2 siRNA could reverse the inhibition of mitophagy by Res through AMPK (adenosine 5'-monophosphate (AMP)-activated protein kinase) and prevent the effect of the mitochondrial permeability transition pore (mPTP) opening. Thus, our data suggest that Res can exert mitochondrial protection by inhibiting mitophagy and preventing mPTP opening through AMPK-Mfn2 axis in myocardial cells.