Resveratrol increases the expression and activity of the low density lipoprotein receptor in hepatocytes by the proteolytic activation of the sterol regulatory element-binding proteins |
| |
Authors: | Yashiro Takuya Nanmoku Manami Shimizu Makoto Inoue Jun Sato Ryuichiro |
| |
Affiliation: | Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan. |
| |
Abstract: | ObjectiveThe hepatocyte low density lipoprotein receptor (LDLR) plays a pivotal role in lipoprotein metabolism by lowering plasma LDL-cholesterol, a risk factor for atherosclerosis. The present study was conducted to investigate the effects of grape polyphenols on LDLR gene expression in human hepatocyte models.Methods and resultsAmong the 14 phenolic compounds in red wine, we found that a stilbene trans-resveratrol most strongly up-regulated LDLR gene expression in HepG2 cells. Trans-resveratrol increased the LDLR protein and uptake of fluorescent-labeled LDL. Moreover, it enhanced LDLR gene promoter activity through the proteolytic activation of the sterol regulatory element-binding protein-2 (SREBP-2) as well as SREBP-1. However, sterols completely abolished trans-resveratrol-induced SREBP activation and LDLR gene expression. Finally, AMP-activated protein kinase (AMPK) knockdown analyses by siRNA revealed that AMPK activation was unnecessary for the effects of trans-resveratrol.ConclusionsTrans-resveratrol up-regulated hepatic LDLR expression via proteolytic activation of SREBPs. We concluded that trans-resveratrol exhibits the anti-atherogenic effect, at least in part, by increased hepatic LDLR expression and subsequent LDL uptake. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|