PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages.
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.
Iida
Kaoruko Tada
KT
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.
Kawakami
Yasushi
Y
Suzuki
Hiroaki
H
Sone
Hirohito
H
Shimano
Hitoshi
H
Toyoshima
Hideo
H
Okuda
Yukichi
Y
Yamada
Nobuhiro
N
D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D003066:Coenzyme A Ligases / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D006904:Hydroxymethylglutaryl-CoA Synthase; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D020218:Response Elements / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists; D000077288:Troglitazone; D015854:Up-Regulation / Q000187:drug effects
D002839:Chromans; D016373:DNA, Antisense; D009841:Oligonucleotides; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D006904:Hydroxymethylglutaryl-CoA Synthase; D003066:Coenzyme A Ligases; D000077288:Troglitazone; D000077205:Pioglitazone