Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury.
Resveratrol is known to be protective against oxidative cardiovascular disorders. However, the underlying mechanisms remain unclear. This study was undertaken to determine if resveratrol could increase endogenous antioxidants and phase 2 enzymes in cardiomyocytes, and if such increased cellular defenses could provide protection against oxidative and electrophilic cell injury. Incubation of cardiac H9C2 cells with low micromolar resveratrol resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. To investigate the protective effects of the resveratrol-induced cellular defenses on oxidative and electrophilic cell injury, H9C2 cells were first incubated with resveratrol, and then exposed to xanthine oxidase (XO)/xanthine, 4-hydroxy-2-nonenal or doxorubicin. We observed that resveratrol pretreatment afforded a marked protection against the above agent-mediated cytotoxicity in H9C2 cells. Moreover, the resveratrol pretreatment led to a great reduction in XO/xanthine-induced intracellular accumulation of ROS. Taken together, this study demonstrates that resveratrol induces antioxidants and phase 2 enzymes in cardiomyocytes, which is accompanied by increased resistance to oxidative and electrophilic cell injury.
Cao
Zhuoxiao
Z
Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Allied Health Professions, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Li
Yunbo
Y
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology*; D002374:Catalase / Q000032:analysis / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000032:analysis / Q000096:biosynthesis; D014969:Xanthine Oxidase / Q000378:metabolism
D000447:Aldehydes; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D000077185:Resveratrol