PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages

Kaoruko Tada Iida; Yasushi Kawakami; Hiroaki Suzuki; Hirohito Sone; Hitoshi Shimano; Hideo Toyoshima; Yukichi Okuda; Nobuhiro Yamada

doi:10.1016/s0014-5793(02)02811-9

PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages

FEBS Lett. 2002 Jun 5;520(1-3):177-81. doi: 10.1016/s0014-5793(02)02811-9.

Authors

Kaoruko Tada Iida¹, Yasushi Kawakami, Hiroaki Suzuki, Hirohito Sone, Hitoshi Shimano, Hideo Toyoshima, Yukichi Okuda, Nobuhiro Yamada

Affiliation

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan.

PMID: 12044893
DOI: 10.1016/s0014-5793(02)02811-9

Abstract

Recently it has been reported that macrophages express a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma). Using a ligand of PPAR gamma, troglitazone or pioglitazone, we have shown that the expression of two genes involved in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were increased by activation of PPAR gamma through a PPAR response element (PPRE) in THP-1 macrophages. In addition, treatment with troglitazone significantly increased the activity of HMG-CoA reductase and the amount of intracellular cholesterol. Thus, we conclude that PPAR gamma and its agonists increase the cholesterol content of macrophages by the increased expression of genes involved in cholesterol biosynthesis. These findings suggest that PPAR gamma may play a role in cholesterol metabolism in macrophages.

Publication types

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

MeSH terms

Cell Differentiation / genetics
Cell Line
Cholesterol / metabolism
Chromans / pharmacology*
Coenzyme A Ligases / genetics*
DNA, Antisense / genetics
DNA, Antisense / pharmacology
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Gene Expression Regulation, Enzymologic / drug effects
Humans
Hydroxymethylglutaryl CoA Reductases / genetics*
Hydroxymethylglutaryl-CoA Synthase
Macrophages / cytology
Macrophages / drug effects*
Macrophages / metabolism
Oligonucleotides / genetics
Oligonucleotides / pharmacology
Pioglitazone
RNA, Messenger / drug effects
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Cytoplasmic and Nuclear / agonists
Response Elements / genetics
Thiazoles / pharmacology*
Thiazolidinediones*
Transcription Factors / agonists
Troglitazone
Up-Regulation / drug effects

Substances

Chromans
DNA, Antisense
Oligonucleotides
RNA, Messenger
Receptors, Cytoplasmic and Nuclear
Thiazoles
Thiazolidinediones
Transcription Factors
Cholesterol
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Synthase
Coenzyme A Ligases
Troglitazone
Pioglitazone