HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.07-103366v1 22/7/2185    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klinge, C. M. Articles by Dougherty, S. M. Search for Related Content PubMed PubMed Citation Articles by Klinge, C. M. Articles by Dougherty, S. M.

Resveratrol stimulates nitric oxide production by increasing estrogen receptor -Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells

Department of Biochemistry and Molecular Biology and the Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA

¹Correspondence: Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA. E-mail: carolyn.klinge{at}louisville.edu

Epidemiological studies correlate moderate red wine consumption to reduced incidence of cardiovascular disease. Resveratrol is a polyphenolic compound in red wine that has cardioprotective effects in rodents. Although endothelial cell (EC) studies indicate that micromolar resveratrol has diverse biological activities, these concentrations are not physiologically relevant because human oral ingestion provides only brief exposure to nanomolar plasma levels. Previously, we reported that nanomolar resveratrol activated ERK1/2 signaling in bovine aortic ECs (BAECs). The goal of this study was to determine the mechanisms by which nanomolar resveratrol rapidly activates endothelial nitric oxide synthase (eNOS) in human umbilical vein ECs (HUVECs). We report for the first time that resveratrol increased interaction between estrogen receptor (ER), caveolin-1 (Cav-1) and c-Src, and increased phosphorylation of Cav-1, c-Src, and eNOS. Pretreatment with the lipid raft disruptor beta-methyl cyclodextrin or G inhibitor pertussis toxin blocked resveratrol- and E₂-induced eNOS activation and NO production. Depletion of endogenous ER, not ERβ, by siRNA attenuated resveratrol- and E₂-induced ERK1/2, Src, and eNOS phosphorylation. Our data demonstrate that nanomolar resveratrol induces ER-Cav-1-c-SRC interaction, resulting in NO production through a G-protein-coupled mechanism. This study provides important new insights into mechanisms for the beneficial effects of resveratrol in ECs.—Klinge, C. M., Wickramasinghe, N. S., Ivanova, M. M., Dougherty, S. M. Resveratrol stimulates nitric oxide production by increasing estrogen receptor -Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells.

Key Words: nongenomic estrogen action • membrane-associated estrogen receptor • red wine polyphenols

This article has been cited by other articles:

				V. Pasciu, A. M. Posadino, A. Cossu, B. Sanna, B. Tadolini, L. Gaspa, A. Marchisio, S. Dessole, G. Capobianco, and G. Pintus Akt Downregulation by Flavin Oxidase-Induced ROS Generation Mediates Dose-Dependent Endothelial Cell Damage Elicited by Natural Antioxidants Toxicol. Sci., March 1, 2010; 114(1): 101 - 112. [Abstract] [Full Text] [PDF]

				Y. Sun, G. Hu, X. Zhang, and R. D. Minshall Phosphorylation of Caveolin-1 Regulates Oxidant-Induced Pulmonary Vascular Permeability via Paracellular and Transcellular Pathways Circ. Res., September 25, 2009; 105(7): 676 - 685. [Abstract] [Full Text] [PDF]