Resveratrol, a phytoestrogen found in red wine, down-regulates protein S expression in HepG2 cells.

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Hiroto Y, Tadokoro K, Tsuda T, Nakazono E, Ohnaka K, Takayanagi R, Hamasaki N, Tsuda H

Resveratrol, a phytoestrogen found in red wine, down-regulates protein S expression in HepG2 cells.

Thromb Res. 2011 Jan;127(1):e1-7. doi: 10.1016/j.thromres.2010.09.010.

PubMed ID
20926118 [ View in PubMed
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Abstract

UNLABELLED: INTRODUATION: Resveratrol, a phytoestrogen present at a high concentration in red wine, has been reported to possess many health benefit effects that are protective against age-related diseases. Protein S (PS), an important anticoagulant factor in the protein C (PC) anticoagulant pathway, is mainly synthesized by hepatocytes, and its plasma level is decreased in high-estrogen conditions such as pregnancy and oral contraceptive use. The aim of this study was to investigate whether resveratrol affects PS expression in HepG2 cells. MATERIALS AND METHODS: The secreted and intracellular levels of PS were determined by an enzyme-linked ligandsorbent assay and Western blotting. The mRNA expressions of PS, PC and beta chain of C4b-binding protein (C4BP-beta) were analyzed by reverse transcription-polymerase chain reaction. The PS gene promotor activities in HepG2 cells transiently expressing estrogen receptor (ER) alpha were examined by a luciferase reporter assay. RESULTS: Resveratrol dose- and time-dependently down-regulated the PS expression in HepG2 cells at a transcriptional level, resulting in a significant decrease in secreted PS; however, the PC and C4BP-beta mRNA expressions were not affected. This action of resveratrol was not mediated through either the ER signaling or those of mitogen-activated protein kinases and protein kinase C. Piceatannol, a hydroxylated metabolite of resveratrol, and genistein, an isoflavone found in soy products, also down-regulated the PS expression. CONCLUSIONS: Resveratrol down-regulates the PS expression in HepG2 cells in an ER-independent manner, and the two phenolic hydroxyls at carbon-3 and -5 of resveratrol may be involved in this function.