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Differential roles for Nrf2 and AP-1 in upregulation of HO-1 expression by arsenite in murine embryonic fibroblasts.

Authors
  • Harada, Harumi
  • Sugimoto, Rika
  • Watanabe, Ayaka
  • Taketani, Shigeru
  • Okada, Kosuke
  • Warabi, Eiji
  • Siow, Richard
  • Itoh, Ken
  • Yamamoto, Masayuki
  • Ishii, Tetsuro
Type
Published Article
Journal
Free Radical Research
Publisher
Informa UK (Taylor & Francis)
Publication Date
Apr 01, 2008
Volume
42
Issue
4
Pages
297–304
Identifiers
DOI: 10.1080/10715760801975735
PMID: 18404528
Source
Medline
License
Unknown

Abstract

Heme oxygenase-1 (HO-1) is markedly upregulated by sodium arsenite and previous studies implicated the transcriptional enhancers Nrf2 and AP-1 in arsenite-induced ho-1 gene expression in murine cells. To further evaluate the role of Nrf2 and its signalling pathway in the induction of HO-1 in response to low levels of arsenite, this paper studied wild-type and Nrf2-deficient murine embryonic fibroblasts. It was found that Nrf2 plays a crucial role in the early activation of ho-1 transcription and that increased Nrf2 levels returned to basal levels within 24 h. In Nrf2(-/-) cells, HO-1 gene activation increased gradually and HO-1 protein levels were approximately half of those attained in Nrf2(+/+) cells. The tyrosine kinase inhibitor genistein and JNK inhibitor SP600125 significantly attenuated arsenite induced increases in ho-1 mRNA levels in Nrf2 deficient cells but had negligible effects on Nrf2 activation, suggesting tyrosine kinase/JNK/c-Jun plays a key role in the HO-1 upregulation via AP-1.

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