PPARγ ligands, troglitazone and pioglitazone, up‐regulate expression of HMG‐CoA synthase and HMG‐CoA reductase gene in THP‐1 macrophages

FEBS Letters

Toyoshima, Hideo¹  Shimano, Hitoshi¹  Suzuki, Hiroaki¹  Iida, Kaoruko Tada¹  Kawakami, Yasushi¹  Sone, Hirohito¹  Yamada, Nobuhiro¹  Okuda, Yukichi¹ 

[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

关键词: Peroxisome proliferator-activated receptor γ;    Troglitazone;    3-Hydroxy-3-methylglutaryl-CoA synthase;    3-Hydroxy-3-methylglutaryl-CoA reductase;    THP-1 cell;    Macrophage;    Pioglitazone;    HMG-CoA;    3-hydroxy-3-methylglutaryl-CoA;    PPAR;    peroxisome proliferator-activated receptor;    PPRE;    PPAR response element;    LDL;    low density lipoprotein;    PMA;    phorbol-12-myristate-13-acetate;    LPL;    lipoprotein lipase;    ACAT;    acyl-CoA:cholesterol acyltransferase;   

DOI  :  10.1016/S0014-5793(02)02811-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently it has been reported that macrophages express a nuclear receptor, peroxisome proliferator-activated receptor γ (PPARγ). Using a ligand of PPARγ, 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 PPARγ 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 PPARγ and its agonists increase the cholesterol content of macrophages by the increased expression of genes involved in cholesterol biosynthesis. These findings suggest that PPARγ may play a role in cholesterol metabolism in macrophages.

【 授权许可】

Unknown