The peroxisome proliferator-activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid omega-hydroxylase, by clofibric acid

• Published in: The Journal of biological chemistry 1992-09, Vol.267 (27), p.19051-19053
• Main Authors: SCOTT MUERHOFF, A, GRIFFIN, K. J, JOHNSON, E. F
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Clofibric Acid - pharmacology; Cloning, Molecular; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Enzyme Induction - drug effects; Fundamental and applied biological sciences. Psychology; Gene expression; Mice; Microbodies - physiology; Mixed Function Oxygenases - biosynthesis; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Promoter Regions, Genetic; Receptors, Cell Surface - genetics; Receptors, Cytoplasmic and Nuclear; Regulatory Sequences, Nucleic Acid; Transcription Factors - genetics; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)41738-3

Gene transfer experiments indicate that induction by the peroxisome proliferators, clofibric acid and WY-14,643, of luciferase expression driven by the promoter and 5'-flanking sequences of the rabbit cytochrome P450 4A6 gene (CYP4A6) is dependent on cotransfection of expression plasmids for the peroxisome proliferator-activated receptor, PPAR. Activation by PPAR is observed in the absence of the inducers. However, a mutant, PPAR-G (Glu282---Gly) activated luciferase expression only in the presence of peroxisome proliferators. Deletion analysis has localized a response element to a 34-base pair segment located 677 base pairs upstream of the CYP4A6 transcription start site that is similar to an element that regulates the response of the rat fatty acyl-CoA oxidase gene to peroxisome proliferators and that binds PPAR.