| Objectives: To examine whether resveratrol protected high glucose-induced cardiacapoptosis through inhibition NADPH oxidase-derived ROS production. Moreover, thesignaling pathway involved in mediating the effect has been explored as well.Methods: Primary cultured neonatal rat cardiomyocytes were exposed to30mmol/Lhigh glucose. Western blot analysis the expression of NADPH oxidase subunits(gp91phox, p47phox, and p67phox) and Rac1, as well as related regulatory factor AMPKwere assessed with or without resveratrol treatment. Western blot analysis theexpression of Bax/Bcl-2. TUNEL detection kit was used to observe apoptosis ofcardiomyocytes according to the manufacturer’s protocol. The intracellular level ofROS were measured using the dihydroethidium (DHE) fluorescence probe, analyzedunder an inverted fluorescence microscopy and HPLC assay.Results: Enhanced Rac1activity and gp91phox, p47phox, p67phoxexpression in highglucose was suppressed by resveratrol. Consistently, the ratio between pro-apoptoticprotein Bax and anti-apoptotic protein Bcl-2was regulated and as a consequence,cardiac cell injury and apoptosis was markedly rescued by resveratrol. In addition,resveratrol significantly increased phosphorylation of AMP-activated protein kinase(AMPK) at Thr172in primary cultured neonatal rat cardiomyocytes subjected to highglucose. Compound C, the pharmacologic inhibitor of AMPK, could mostly abrogatethese roles of resveratrol on cardiomyocytes in high glucose.Conclusions: Our data demonstrate that resveratrol may have therapeutic potential fordiabetic cardiomyopathy by attenuating oxidative stress and preventing myocardialapoptosis, and this effect is mostly mediated by AMPK signaling pathway. |
