Ligand- and species-dependent activation of PPARalpha.
Peroxisome proliferator-activated receptor alpha (PPARalpha) is mainly expressed in liver and involved in lipid metabolism. Oxidation of certain fatty acids in peroxisomes is under PPARalpha control. A wide variety of lipid molecules activate PPARalpha as well as the fibric acid derivative clofibrate. In the present study, we evaluated the differential activation of PPARalpha with several agonist ligands through its expression and DNA binding in both rat (McA-RH7777) and human (HepG2) hepatoma cell lines. In McA-RH7777 cells, clofibrate alone mediated a higher induction of PPARalpha expression than linoleic acid. In contrast, linoleic acid was the most effective ligand in HepG2 cells and treatment with clofibrate plus linoleic acid did not further increase PPARalpha expression. PPRE-binding activity of PPARalpha in ligand-treated cells was also increased in a parallel manner. We suggest that ligand-induced PPARalpha activation might give rise to differential species-dependent responses.
Hacettepe University Faculty of Medicine, Department of Biochemistry, Ankara, Turkey. fakbiyik@hacettepe.edu.tr
Filiz
F
Akbiyik
Denise M
DM
Ray
Hakan
H
Bozkaya
Ediz
E
Demirpence
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D002994:Clofibrate / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008024:Ligands; D019787:Linoleic Acid / Q000494:pharmacology / Q000502:physiology; D008099:Liver / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000032:analysis / Q000502:physiology; D051381:Rats; D013045:Species Specificity
D005231:Fatty Acids, Unsaturated; D008024:Ligands; D047493:PPAR alpha; D004247:DNA; D019787:Linoleic Acid; D002994:Clofibrate