Quercetin protects the hydrogen peroxide-induced apoptosis via inhibition of mitochondrial dysfunction in H9c2 cardiomyoblast cells.
Quercetin possesses a broad range of pharmacological properties, including protection of LDL from oxidation. However, little is known about the mechanism by which quercetin rescues cardiomyoblasts from oxidative damage. This study was designed to investigate the protective mechanism of quercetin on H(2)O(2)-induced toxicity of H9c2 cardiomyoblasts. Oxidative stress, such as H(2)O(2), ZnCl(2), and menadione, significantly decreased the viability of H9c2 cells, which was accompanied with apparent apoptotic features, including fragmentation of genomic DNA as well as activation of caspase protease. However, quercetin markedly inhibited the apoptotic characteristics via reduction of intracellular reactive oxygen species generation. Also, it prevented the H(2)O(2)-mediated mitochondrial dysfunction, including disruption of mitochondria membrane permeability transition as well as an increase in expression of apoptogenic Bcl-2 proteins, Bcl-2 and Bcl-X(L). Furthermore, pretreatment of quercetin inhibited the activation of caspase-3, thereby both cleavage of poly(ADP-ribose) polymerase and degradation of inhibitor of caspase-activated DNase/DNA fragmentation factor by H(2)O(2) were completely abolished. Taken together, these data suggest that protective effects of quercetin against oxidative injuries of H9c2 cardiomyoblasts may be achieved via modulation of mitochondrial dysfunction and inhibition of caspase activity.
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D011794:Quercetin; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases