Exacerbation of tobacco smoke mediated apoptosis by resveratrol: an unexpected consequence of its antioxidant action.
Resveratrol, a polyphenolic compound rich in grapes and red wine, has been reported to protect cells against oxidative damage and cell death by increasing cellular antioxidant/detoxification capacity. Cigarette smoking is a major risk factor for respiratory diseases and oxidative damage is implicated in its pathogenesis. Here we investigated the enhancement of antioxidant capacity by resveratrol and its potential protection against cell death caused by cigarette smoke in human bronchial epithelial cells (HBE1). At concentrations that did not affect cell growth, resveratrol activated Nrf2 signaling and increased the expression of NAD(P)H:quinone reductase-1, heme oxygenase-1, and the catalytic subunit of glutamate cysteine ligase. Surprisingly, instead of protecting against cell death, resveratrol significantly enhanced cigarette smoke extract-induced apoptosis. To define the underlying mechanism, the effect of resveratrol on caspase activity was examined and it was found that resveratrol significantly enhanced cigarette smoke-stimulated caspase activity. In conclusion, results from this study suggest that although resveratrol increased antioxidant and detoxification capacity, it increased rather than protected against cigarette smoke-induced apoptosis.
Zhang
Hongqiao
H
School of Natural Sciences, University of California at Merced, Merced, CA 95343, United States. hzhang@ucmerced.edu
Shih
Albert
A
Rinna
Alessandra
A
Forman
Henry Jay
HJ
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology; D053148:Caspase 3 / Q000187:drug effects*; D053453:Caspase 9 / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D012907:Smoking / Q000009:adverse effects; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D053148:Caspase 3; D053453:Caspase 9; D005721:Glutamate-Cysteine Ligase; D000077185:Resveratrol