High density lipoprotein inhibits the activation of sterol regulatory element-binding protein-1 in cultured cells

Masaki Yoshida; Nagakatsu Harada; Keiko Yoshida; Tadahiko Nakagawa; Takaaki Shimohata; Kazuaki Mawatari; Akira Takahashi; Hiroshi Sakaue; Yutaka Nakaya

doi:10.1016/j.febslet.2010.02.034

High density lipoprotein inhibits the activation of sterol regulatory element-binding protein-1 in cultured cells

FEBS Lett. 2010 Mar 19;584(6):1217-22. doi: 10.1016/j.febslet.2010.02.034. Epub 2010 Feb 18.

Authors

Masaki Yoshida¹, Nagakatsu Harada, Keiko Yoshida, Tadahiko Nakagawa, Takaaki Shimohata, Kazuaki Mawatari, Akira Takahashi, Hiroshi Sakaue, Yutaka Nakaya

Affiliation

¹ Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima-city, Japan. zyousyou8@yahoo.co.jp

PMID: 20171215
DOI: 10.1016/j.febslet.2010.02.034

Abstract

A link between cellular uptake of high density lipoprotein (HDL) and regulation of sterol regulatory element-binding protein-1 (SREBP-1) was investigated in vitro. HDL decreased nuclear SREBP-1 levels as well as SREBP-1 target gene expression in HepG2 and HEK293 cells. However, HDL did not repress an exogenously expressed, constitutively active form of SREBP-1. HDL increased cellular cholesterol levels, and cellular cholesterol depletion by methyl-beta-cyclodextrin abolished the effects of HDL. These results suggest that HDL inhibits the activation of SREBP-1 through a cholesterol-dependent mechanism, which may play an important role in regulating lipid synthetic pathways mediated by SREBP-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyl-CoA Carboxylase / genetics
Acetyl-CoA Carboxylase / metabolism
Animals
Cells, Cultured
Fatty Acid Synthases / genetics
Fatty Acid Synthases / metabolism
Gene Expression Regulation, Enzymologic / drug effects
Hep G2 Cells
Humans
Lipid Metabolism / drug effects
Lipid Metabolism / genetics
Lipoproteins, HDL / pharmacology*
Male
Promoter Regions, Genetic / drug effects
Rats
Rats, Sprague-Dawley
Stearoyl-CoA Desaturase / genetics
Stearoyl-CoA Desaturase / metabolism
Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors*
Sterol Regulatory Element Binding Protein 1 / genetics
Sterol Regulatory Element Binding Protein 1 / metabolism
Sterol Regulatory Element Binding Protein 1 / physiology
Transcriptional Activation / drug effects*

Substances

Lipoproteins, HDL
Sterol Regulatory Element Binding Protein 1
Stearoyl-CoA Desaturase
Fatty Acid Synthases
Acetyl-CoA Carboxylase