Journal
ATHEROSCLEROSIS
Volume 220, Issue 2, Pages 369-374Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2011.11.006
Keywords
LDL receptor; Resveratrol; SREBP
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
Ask authors/readers for more resources
Objective: The 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 results: Among 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. Conclusions: Trans-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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available