Reference - Detail
|Author||Hiroto Y, Tadokoro K, Tsuda T, Nakazono E, Ohnaka K, Takayanagi R, Hamasaki N, Tsuda H.|
|Title||Resveratrol, a phytoestrogen found in red wine, down-regulates protein S expression in HepG2 cells.|
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.
|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*|
|WOS Category||HEMATOLOGY PERIPHERAL VASCULAR DISEASE|
|Human and Animal Cells|