Exp Mol Med.
2008 Dec;40(6):658-668. 10.3858/emm.2008.40.6.658.
CD36 signaling inhibits the translation of heat shock protein 70 induced by oxidized low density lipoprotein through activation of peroxisome proliferators-activated receptor gamma
- Affiliations
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- 1Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chunchon, Korea. jhahn@kangwon.ac.kr
- 2Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
- 3Department of Biochemistry, College of Natural Science, Kangwon National University, Chunchon, Korea.
- 4Department of Pediatrics, Chung-Ang University, Seoul, Korea.
- 5Department of Anatomy, School of Medicine, Sungkyunkwan University, Suwon, Korea.
- 6Vascular System Research Center, Kangwon National University, Chunchon, Korea.
- KMID: 1072946
- DOI: http://doi.org/10.3858/emm.2008.40.6.658
Abstract
- Oxidized LDL (OxLDL), a causal factor in atherosclerosis, induces the expression of heat shock proteins (Hsp) in a variety of cells. In this study, we investigated the role of CD36, an OxLDL receptor, and peroxisome proliferator-activated receptor gamma (PPAR gamma) in OxLDL-induced Hsp70 expression. Overexpression of dominant-negative forms of CD36 or knockdown of CD36 by siRNA transfection increased OxLDL-induced Hsp70 protein expression in human monocytic U937 cells, suggesting that CD36 signaling inhibits Hsp70 expression. Similar results were obtained by the inhibition of PPAR gamma activity or knockdown of PPAR gamma expression. In contrast, overexpression of CD36, which is induced by treatment of MCF-7 cells with troglitazone, decreased Hsp70 protein expression induced by OxLDL. Interestingly, activation of PPAR gamma through a synthetic ligand, ciglitazone or troglitazone, decreased the expression levels of Hsp70 protein in OxLDL-treated U937 cells. However, major changes in Hsp70 mRNA levels were not observed. Cycloheximide studies demonstrate that troglitazone attenuates Hsp70 translation but not Hsp70 protein stability. PPAR gamma siRNA transfection reversed the inhibitory effects of troglitazone on Hsp70 translation. These results suggest that CD36 signaling may inhibit stress- induced gene expression by suppressing translation via activation of PPAR gamma in monocytes. These findings reveal a new molecular basis for the anti-inflammatory effects of PPAR gamma.
Keyword
MeSH Terms
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Antigens, CD36/*physiology
Cell Line, Tumor
Chromans/pharmacology
Cycloheximide/pharmacology
HSP70 Heat-Shock Proteins/*biosynthesis
Humans
Lipoproteins, LDL/pharmacology/*physiology
Monocytes/drug effects/metabolism
PPAR gamma/agonists/antagonists & inhibitors/*physiology
Protein Synthesis Inhibitors/pharmacology
Signal Transduction
Thiazolidinediones/pharmacology
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