Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Regulation of p450 4a expression by peroxisome proliferator activated receptors

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Johnson, Eric
  • Hsu, M. H.
  • Savas, U.
  • Griffin, K. J.

publication date

  • December 2002

journal

  • Toxicology  Journal

abstract

  • The induction of P450 4A enzymes by peroxisome proliferators (PPs) and fatty acids is mediated by the peroxisome proliferator activated receptor alpha (PPAR alpha) that binds to response elements in target genes as a heterodimer with the retinoid X receptor (RXR). The consensus sequence recognized by PPAR/RXR heterodimers, contains an imperfect direct repeat of two nuclear receptor binding motifs separated by a single nucleotide. This repeat is preceded by a conserved A/T rich sequence that is required for function. In mice, chronic exposure to PPs results in PPAR alpha mediated liver hypertrophy, hyperplasia and carcinogenesis accompanied by a proliferation of peroxisomes. In contrast, humans exhibit a reduced sensitivity to PP pathogenesis. This could reflect >10-fold lower PPAR alpha levels relative to mice as well as differences in targeted genes. In order to identify PPAR responsive human genes, the human hepatoma cell line, HepG2, was engineered to express increased levels of PPAR alpha. Several genes encoding rate-limiting enzymes and branch points in ketone body formation are regulated by PPAR alpha in these cells. In contrast, significant induction by PP is not evident for peroxisomal fatty acid oxidation that is associated with peroxisome proliferation in mice. Human P450 4A11 is not expressed in dividing cultures of cells with enhanced PPAR alpha levels, but it is expressed in confluent cultures expressing elevated amounts of PPAR alpha.

subject areas

  • Animals
  • Cytochrome P-450 CYP4A
  • Cytochrome P-450 Enzyme System
  • Fatty Acids
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Mixed Function Oxygenases
  • Peroxisome Proliferators
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Drug
  • Species Specificity
  • Transcription Factors
scroll to property group menus

Research

keywords

  • CYP4A
  • fatty acid oxidation
  • gene regulation
  • ketogenesis
  • peroxisome proliferation
  • peroxisome proliferator activated receptor, PPAR
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0300-483X

Digital Object Identifier (DOI)

  • 10.1016/s0300-483x(02)00282-2

PubMed ID

  • 12505311
scroll to property group menus

Additional Document Info

start page

  • 203

end page

  • 206

volume

  • 181

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support