Resveratrol, a polyphenol found in fruits, has been demonstrated to activate Sir2. Though many studies have demonstrated that resveratrol can activate SIRT1, whether it has effect on other sirtuins (SIRT2-7) are unknown. The present study shows that exposure of H9c2 cells to 50 mu M H2O2 for 6 h caused a significant increase in apoptosis, as evaluated by TUNEL and flow cytometry (FCM), but pretreatment of resveratrol (20 mu M) eliminated H2O2-induced apoptosis. Resveratrol also prevented H2O2-induced caspase-3 activation. Exposure of cells to resveratrol caused rapid activation of SIRT1,3,4,7. Sirtuin inhibitor, nicotinamide (20 mM) attenuated resveratrol's inhibitory effect on cell apoptosis and caspase-3 activity. These results suggest that resveratrol protects cardiomyocytes from H2O2-induced apoptosis by activating SIRT1,3,4,7. J. Cell. Biochem. 107: 741-747, 2009. (C) 2009 Wiley-Liss, Inc.