title: CD36 signaling inhibits the translation of heat shock protein 70 induced by oxidized low density lipoprotein through activation of peroxisome proliferators-activated receptor gamma.
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 (PPARgamma) 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 PPARgamma activity or knockdown of PPARgamma 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 PPARgamma 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. PPARgamma 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 PPARgamma in monocytes. These findings reveal a new molecular basis for the anti-inflammatory effects of PPARgamma.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chunchon 200-701, Korea.
authors.forename: Kyoung Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Ha
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Suh
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyeong Han
authors.initials: KH
authors.lastname: Park
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Dongmin
authors.initials: D
authors.lastname: Kang
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Kim
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
authors.forename: Young Kyoun
authors.initials: YK
authors.lastname: Kim
authors.forename: Ho Dirk
authors.initials: HD
authors.lastname: Kim
authors.forename: Jang Hee
authors.initials: JH
authors.lastname: Hahn
mesh_terms: D018955:CD36 Antigens / Q000502:physiology*; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D018955:CD36 Antigens; D002839:Chromans; D018840:HSP70 Heat-Shock Proteins; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D011500:Protein Synthesis Inhibitors; D045162:Thiazolidinediones; C099252:oxidized low density lipoprotein; D003513:Cycloheximide; D000077288:Troglitazone; C039671:ciglitazone