Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD.
trans-Resveratrol (3,4',5-trihydroxystilbene; RES), a polyphenol found in particularly high concentrations in red wine, has recently attracted intense interest for its potentially beneficial effects on human health. Here, we report the effects of long-term exposure to micromolar concentrations of RES on antioxidant and DNA repair enzyme activities in a human cell line (MRC-5). RES had either no effect on, or reduced the activities of glutathione peroxidase, catalase and CuZn superoxide dismutase (SOD), in treatments lasting up to 2 weeks. RES failed to induce activities of the DNA base excision repair enzymes apurinic/apyrimidinic endonuclease and DNA polymerase beta. However, it dramatically and progressively induced mitochondrial MnSOD expression and activity. Two weeks exposure to RES increased MnSOD protein level 6-fold and activity 14-fold. Thus, long-term exposure of human cells to RES results in a highly specific upregulation of MnSOD, and this may be an important mechanism by which it elicits its effects in human cells.
Robb
Ellen L
EL
Department of Biological Sciences, Brock University, 500 Glenridge Road, St. Catharines, Ont., Canada L2S 3A1.
Page
Melissa M
MM
Wiens
Brent E
BE
Stuart
Jeffrey A
JA
D000975:Antioxidants / Q000008:administration & dosage; D002460:Cell Line; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D029968:Escherichia coli Proteins; D013267:Stilbenes; D013482:Superoxide Dismutase; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D000077185:Resveratrol