Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells.
Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities. One of the plausible ways to prevent the reactive oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of endogenous antioxidant defense capacity. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), one of the major antioxidative constituents found in the skin of grapes, has been considered to be responsible in part for the protective effects of red wine consumption against coronary heart disease ('French Pardox'). In this study, we have investigated the effects of resveratrol on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with hydrogen peroxide underwent apoptotic death as determined by characteristic morphological features, internucleosomal DNA fragmentation and positive in situ end-labeling by terminal transferase (TUNEL staining). Resveratrol pretreatment attenuated hydrogen peroxide-induced cytotoxicity, DNA fragmentation, and intracellular accumulation of ROS. Hydrogen peroxide transiently induced activation of NF-kappaB in PC12 cells, which was mitigated by resveratrol pretreatment. These results suggest that resveratrol has the potential to prevent oxidative stress-induced cell death.
Jang
J H
JH
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, 151-742, Seoul, South Korea.
Surh
Y J
YJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D016328:NF-kappa B / Q000096:biosynthesis; D009707:Nucleosomes / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D016328:NF-kappa B; D009707:Nucleosomes; D017382:Reactive Oxygen Species; D013267:Stilbenes; D006861:Hydrogen Peroxide; D000077185:Resveratrol