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

研究成果: Article査読

1209 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)16023-16029
ページ数7
ジャーナルJournal of Biological Chemistry
275
21
DOI
出版ステータスPublished - 2000 5月 26
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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