期刊
AMERICAN JOURNAL OF CLINICAL NUTRITION
卷 77, 期 5, 页码 1220-1228出版社
OXFORD UNIV PRESS
DOI: 10.1093/ajcn/77.5.1220
关键词
resveratrol; endothelial cells; nuclear factor-kappa B; atherosclerosis; inflammatory disease; red wine; tumor necrosis factor alpha
Background: Resveratrol (a naturally occurring phytoalexin found in grapes and wine) has cardiovascular protective effects that suggest the antiatherogenic (ie, anti inflammatory) activities of the compound on endothelial cells. Objective: The antiinflammatory activity of resveratrol could be mediated by its interference with nuclear factor-kappaB (NF-kappaB)-dependent transcription. Thus, we studied the in vitro influence of physiologic concentrations of resveratrol (less than or equal to 1 mumol/L) on the NF-kappaB signaling pathway after tumor necrosis factor alpha (TNF-alpha) stimulation of endothelial cells. Design: The effects of a 30-min (acute) and an overnight incubation of resveratrol on the nuclear appearance of p50-NF-kappaB and p65-NF-kappaB on serine and tyrosine phosphorylation of the inhibitory subunit kappaB alpha (IkappaBalpha), cytoplasmic concentrations of IkappaBalpha, NF-kappaB phosphorylation or nitrosylation, the reduction of the mitotic inhibitor p21, and the activation of peroxisome proliferator-activated receptor a were evaluated. Results: The nuclear appearance of p50-NFkappaB and p65-NFkappaB acutely induced by TNF-alpha. was not modified by resveratrol but was increased after overnight incubation with resveratrol alone or in combination with TNF-alpha. Acute treatment with resveratrol did not modify TNF-alpha-induced cytoplasmic IkappaBalpha serine phosphorylation but did increase IkappaBalpha tyrosine phyophorylation. Resveratrol increased the tyrosine phosphorylation (but not nitrosylation) of immunoprecipitated NF-kappaB, did not decrease cellular p21, and did not increase peroxisome proliferator-activated receptor alpha activity. Conclusions: Acute resveratrol treatment does not inhibit the nuclear appearance of NF-kappaB in human umbilical vein endothelial cells, but overnight treatment does. The increase in tyrosine phosphorylation of IkappaBalpha, p50-NF-kappaB, and p65-NF-kappaB suggests the involvement of such alterations in the modulation of NF-kappaB transcription activity.
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