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KMID : 0620920080400060658
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Experimental & Molecular Medicine
2008 Volume.40 No. 6 p.658 ~ p.668
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CD36 signaling inhibits the translation of heat shock protein 70 induced by oxidized low density lipoprotein through activation of peroxisome proliferators-activated receptor γ
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Lee Kyoung-Jin
Jeoung Doo-Il
Kim Byung-Chul
Kim Min-Kyoung
Hahn Jang-Hee
Park Jeong-Hyun
Kim Dae-Joong
Kim Ho-Dirk
Ha Eun-Soo
Lee Sang-Hoon
Suh Jae-Sung
Lee Sun-Hee
Park Kyeong-Han
Kang Dong-Min
Kim Young-Kyoun
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Abstract
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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 ? (PPAR?) 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? activity or knockdown of PPAR? 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? 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? 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 PPARg in monocytes. These findings reveal a new molecular basis for the anti-inflammatory effects of PPAR.
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KEYWORD
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antigens, CD36, HSP70 heat-shock proteins, oxidized low density lipoprotein, PPARγ, protein biosynthesis
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