Central role of PPARalpha in the mechanism of action of hepatocarcinogenic peroxisome proliferators.
Peroxisome proliferators (PP) are a large class of structurally dissimilar chemicals. These chemicals have diverse effects in rodents and humans, including regulation of lipid metabolism, growth promotion, and induction of hepatocarcinogenesis. Most, if not all, effects of PP are mediated by three members of the nuclear receptor superfamily called PP-activated receptors (PPAR). In this review, we discuss the evidence that PPARalpha, the predominant PPAR in the, liver is involved in the growth promoting and hepatocarcinogenic effects of PP.
Corton
J C
JC
Chemical Industry Institute of Toxicology (CIIT), P.O. Box 12137, 6 Davis Drive, Research Triangle Park, NC 27709-2137, USA. corton@ciit.org
Lapinskas
P J
PJ
Gonzalez
F J
FJ
D042962:Acyl-CoA Oxidase; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000139:chemically induced*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010088:Oxidoreductases / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D018570:Risk Assessment; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D009687:Nuclear Proteins; D020025:Peroxisome Proliferators; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D042926:Cytochrome P-450 CYP4A; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase