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Cholesteryl ester hydroperoxides increase macrophage CD36 gene expression via PPAR{alpha}

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [3];  [1];  [3];  [4];  [3];  [5]
  1. CNRS, UMR 8601, Laboratoire de Chimie-Physique, Paris F-75006 (France)
  2. INSERM, U551, Paris F-75013 (France)
  3. Universite Paris Descartes, Faculte de Pharmacie, Laboratoire de Biochimie Metabolique et Clinique (EA 3617), Paris F-75006 (France)
  4. INSERM, U747, Laboratoire de Pharmacologie, Toxicologie et Signalisation Moleculaire, Paris F-75006 (France)
  5. INSERM, U747, Laboratoire de Pharmacologie, Toxicologie et Signalisation Moleculaire, Paris F-75006 (France) and Universite Paris Descartes, Paris F-75006 (France)
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 PPAR{alpha} or {gamma}. Electrophoretic-mobility-shift-assays with nuclear extracts prepared from macrophages treated by either oxidized LDL or CEOOH showed increased binding of PPAR{alpha} to the CD36 gene promoter PPRE. In conclusion, CEOOH present in oxidized LDL increase CD36 gene expression in a pathway involving PPAR{alpha}.
OSTI ID:
20857931
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 351; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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