Cholesteryl ester hydroperoxides increase macrophage CD36 gene expression via PPARalpha.
The uptake of oxidized LDL by macrophages is a key event in the development of atherosclerosis. The scavenger receptor CD36 is one major receptor that internalizes oxidized LDL. In differentiated human macrophages, we compared the regulation of CD36 expression by copper-oxidized LDL or their products. Only oxidized derivatives of cholesteryl ester (CEOOH) increased the amount of CD36 mRNA (2.5-fold). Both oxidized LDL and CEOOH treatment increased two to fourfold the transcription of promoters containing peroxisome-proliferator-activated-receptor responsive elements (PPRE) in the presence of PPARalpha or gamma. Electrophoretic-mobility-shift-assays with nuclear extracts prepared from macrophages treated by either oxidized LDL or CEOOH showed increased binding of PPARalpha to the CD36 gene promoter PPRE. In conclusion, CEOOH present in oxidized LDL increase CD36 gene expression in a pathway involving PPARalpha.
Jedidi
Iness
I
CNRS, UMR 8601, Laboratoire de Chimie-Physique, Paris F-75006, France.
Couturier
Martine
M
Thérond
Patrice
P
Gardès-Albert
Monique
M
Legrand
Alain
A
Barouki
Robert
R
Bonnefont-Rousselot
Dominique
D
Aggerbeck
Martine
M
D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism*
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D047493:PPAR alpha; C099252:oxidized low density lipoprotein; C081459:cholesteryl ester hydroperoxide