TY - JOUR
T1 - Resveratrol, a phytoestrogen found in red wine, down-regulates protein S expression in HepG2 cells
AU - Hiroto, Yoshie
AU - Tadokoro, Kana
AU - Tsuda, Tomohide
AU - Nakazono, Eri
AU - Ohnaka, Keizo
AU - Takayanagi, Ryoichi
AU - Hamasaki, Naotaka
AU - Tsuda, Hiroko
N1 - Funding Information:
We would like to thank Dr. Shigeaki Kato (University of Tokyo, Tokyo, Japan) for providing plasmids, pSG5-ERα and pERE2-tk109-LUC. We also thank Ms. S. Kitamura for technical assistance and undergraduate students, M. Ariyoshi, M. Abe, S. Shinozaki, C. Watanabe, A. Toyozumi, T. Matsuyama, and M. Kishikawa for contributing to the preliminary experiments. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Nos. 15500560 and 18500639 to HT), a Grant-in-Aid for the Comprehensive Research on Aging and Health from the Ministry of Health, Labor and Welfare (H16-Choju-009 to RT) and by a grant from Nakamura Gakuen University (to HT).
PY - 2011/1
Y1 - 2011/1
N2 - 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 β chain of C4b-binding protein (C4BP-β) were analyzed by reverse transcription-polymerase chain reaction. The PS gene promotor activities in HepG2 cells transiently expressing estrogen receptor (ER) α 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-β 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.
AB - 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 β chain of C4b-binding protein (C4BP-β) were analyzed by reverse transcription-polymerase chain reaction. The PS gene promotor activities in HepG2 cells transiently expressing estrogen receptor (ER) α 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-β 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.
UR - http://www.scopus.com/inward/record.url?scp=78650512503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650512503&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2010.09.010
DO - 10.1016/j.thromres.2010.09.010
M3 - Article
C2 - 20926118
AN - SCOPUS:78650512503
VL - 127
SP - e1-e7
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 1
ER -