Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts.
Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression of tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol.
Wang
Zhirong
Z
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Chen
Yan
Y
Labinskyy
Nazar
N
Hsieh
Tze-chen
TC
Ungvari
Zoltan
Z
Wu
Joseph M
JM
D001011:Aorta / Q000166:cytology; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis; D002316:Cardiotonic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003576:Electron Transport Complex IV / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D027843:Vitis / Q000737:chemistry*; D014920:Wine
D051033:Apoptosis Inducing Factor; D002316:Cardiotonic Agents; D006360:Heat-Shock Proteins; D010936:Plant Extracts; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D052250:Nitric Oxide Synthase Type III; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D003576:Electron Transport Complex IV; D048049:Extracellular Signal-Regulated MAP Kinases; D000077185:Resveratrol