Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages

Tetsuro Ishii, Ken Itoh, Satoru Takahashi, Hideyo Sato, Toru Yanagawa, Yasutake Katoh, Shiro Bannai, Masayuki Yamamoto

Research output: Contribution to journalArticle

1104 Citations (Scopus)

Abstract

Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator of one defense mechanism against such havoc. Nrf2 regulates the inducible expression of a group of detoxication enzymes, such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that Nrf2 also controls the expression of a group of electrophile-and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system x(c)/-) activity. The response to electrophilic and reactive oxygen species-producing agents was profoundly impaired in Nrf2-deficient cells. The lack of induction of system x(c)/- activity resulted in the minimum level of intracellular glutathione, and Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2 regulates a wide-ranging metabolic response to oxidative stress.

Original languageEnglish
Pages (from-to)16023-16029
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number21
DOIs
Publication statusPublished - 2000 May 26

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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