CD36 signaling inhibits the translation of heat shock protein 70 induced by oxidized low density lipoprotein through activation of peroxisome proliferators-activated receptor gamma.
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.
Lee
Kyoung Jin
KJ
Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chunchon 200-701, Korea.
Ha
Eun Soo
ES
Kim
Min Kyoung
MK
Lee
Sang Hoon
SH
Suh
Jae Sung
JS
Lee
Sun Hee
SH
Park
Kyeong Han
KH
Park
Jeong Hyun
JH
Kim
Dae Joong
DJ
Kang
Dongmin
D
Kim
Byung Chul
BC
Jeoung
Dooil
D
Kim
Young Kyoun
YK
Kim
Ho Dirk
HD
Hahn
Jang Hee
JH
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
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