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PMID: 1326542 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of biological chemistry ·Vol. 267 ·No. 27 ·1992-09-25 ·Pages 19051-3

Muerhoff AS, Griffin KJ, Johnson EF

Abstract

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.

Related Genes
MeSH Terms
Animals Base Sequence Clofibric Acid/pharmacology Cloning, Molecular Cytochrome P-450 CYP4A Cytochrome P-450 Enzyme System/biosynthesis,genetics,metabolism Enzyme Induction/drug effects Mice Microbodies/physiology Mixed Function Oxygenases/biosynthesis,genetics,metabolism Molecular Sequence Data Promoter Regions, Genetic Receptors, Cell Surface/genetics Receptors, Cytoplasmic and Nuclear Regulatory Sequences, Nucleic Acid Transcription Factors/genetics Transfection
Chemicals
Receptors, Cell Surface Receptors, Cytoplasmic and Nuclear Transcription Factors Clofibric Acid Cytochrome P-450 Enzyme System Mixed Function Oxygenases Cytochrome P-450 CYP4A
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Muerhoff A S
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Griffin K J
Johnson E F
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
Published
1992-09-25
Pages
19051-3
Language
English
Region
United States
NLM ID
2985121R
Subset
IM
Grants
NICHD NIH HHS · HD04445 · United States
NCRR NIH HHS · M01 RR00833 · United States
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