Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein 1 in mouse embryo fibroblasts

Asako Hayashi, Hiroshi Suzuki, Ken Itoh, Masayuki Yamamoto, Yuichi Sugiyama

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

The nuclear factor-E2 p45-related factor (Nrf) 2 is a transcription factor for the antioxidant responsive element-mediated induction of enzymes responsible for conjugation. Since multidrug resistance-associated protein1 (Mrp1/Abcc1) is an ATP-binding cassette transporter which plays an important role in the cellular extrusion of conjugated metabolites and, therefore, acts synergistically with conjugating enzymes for the cellular detoxification of xenobiotics, we examined the possibility that Nrf2 is also involved in the expression of Mrp1 in mouse embryo fibroblasts. The constitutive expression levels of Mrp1 mRNA and protein were significantly lower in Nrf2 (-/-) cells compared with those in wild type cells. In addition, significant induction by diethyl maleate was observed in wild type, but not in Nrf2 (-/-), cells, suggesting the involvement of Nrf2 in both the constitutive and inducible mRNA and protein expression of Mrp1. In addition, the uptake of [ 3H]2,4-dinitrophenyl-S-glutathione, a typical substrate of Mrp1, into isolated membrane vesicles also demonstrated that Nrf2 regulates the transport activity of glutathione conjugates in mouse fibroblasts. This is the first demonstration that Nrf2 is required for the constitutive and inducible expression of Mrp family proteins.

Original languageEnglish
Pages (from-to)824-829
Number of pages6
JournalBiochemical and biophysical research communications
Volume310
Issue number3
DOIs
Publication statusPublished - 2003 Oct 24
Externally publishedYes

Keywords

  • Induction
  • Mrp1
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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