論文 - 詳細
RRC ID | 38568 |
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著者 | Hiroto Y, Tadokoro K, Tsuda T, Nakazono E, Ohnaka K, Takayanagi R, Hamasaki N, Tsuda H. |
タイトル | Resveratrol, a phytoestrogen found in red wine, down-regulates protein S expression in HepG2 cells. |
ジャーナル | Thromb Res |
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 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. |
巻・号 | 127(1) |
ページ | e1-7 |
公開日 | 2011-1-1 |
DOI | 10.1016/j.thromres.2010.09.010 |
PII | S0049-3848(10)00483-4 |
PMID | 20926118 |
MeSH | Blood Proteins / genetics Blood Proteins / metabolism* Blotting, Western Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Dose-Response Relationship, Drug Down-Regulation Enzyme-Linked Immunosorbent Assay Estrogen Receptor alpha / metabolism Gene Expression Regulation, Neoplastic / drug effects Genistein / pharmacology Hep G2 Cells Histocompatibility Antigens / metabolism Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism* Molecular Structure Phytoestrogens / chemistry Phytoestrogens / pharmacology* Promoter Regions, Genetic / drug effects Protein C / metabolism Protein S / genetics Protein S / metabolism* RNA, Messenger / metabolism Resveratrol Reverse Transcriptase Polymerase Chain Reaction Stilbenes / chemistry Stilbenes / pharmacology* Structure-Activity Relationship Time Factors Transcription, Genetic / drug effects Transfection Wine* |
IF | 2.869 |
引用数 | 13 |
WOS 分野 | HEMATOLOGY PERIPHERAL VASCULAR DISEASE |
リソース情報 | |
ヒト・動物細胞 |