Oxidized phospholipids activate PPARα in a phospholipase A2‐dependent manner

FEBS Letters

Staels, Bart¹  Teissier, Elisabeth¹  Delerive, Philippe¹  Furman, Christophe¹  Fruchart, Jean-Charles¹  Duriez, Patrick¹ 

[1] INSERM U.325, Département d'Athérosclérose, Institut Pasteur de Lille, 1 Rue Calmette, P.O. Box 245, 59019 Lille, France

关键词: Peroxisome proliferator-activated receptor;    Phospholipid;    Phospholipase A2;    Oxidized low-density lipoprotein;   

DOI  :  10.1016/S0014-5793(00)01364-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The peroxisome proliferator-activated receptor α (PPARα) is a transcription factor belonging to the PPAR subfamily of nuclear receptors. Fatty acids and eicosanoids are natural PPARα ligands. Here, we show using transient transfection assays that oxidized (oxLDL) but not native low-density lipoproteins (LDL) dose-dependently activate PPARα in endothelial cells without affecting PPARα protein expression. Fractioning of oxLDL lipids followed by transactivation experiments demonstrated that the oxidized phospholipid component in oxLDL is responsible for PPARα activation. Using specific inhibitors, it is shown that oxLDL-mediated PPARα activation requires phospholipase A2 activity and that the oxidized fatty acids 9- and 13-HODE activate PPARα directly. Finally, we found that, similar to the synthetic PPARα ligand Wy-14643, oxLDL induced expression of the fatty acid transport protein-1 in human primary endothelial cells. Our findings define a novel group of PPARα activators and provide a molecular basis for certain effects of these biologically active phospholipids on gene transcription.

【 授权许可】

Unknown