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

Harumi Harada; Rika Sugimoto; Ayaka Watanabe; Shigeru Taketani; Kosuke Okada; Eiji Warabi; Richard Siow; Ken Itoh; Masayuki Yamamoto; Tetsuro Ishii

doi:10.1080/10715760801975735

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

Harumi Harada, Rika Sugimoto, Ayaka Watanabe, Shigeru Taketani, Kosuke Okada, Eiji Warabi, Richard Siow, Ken Itoh, Masayuki Yamamoto, Tetsuro Ishii

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

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.

Original language	English
Pages (from-to)	297-304
Number of pages	8
Journal	Free Radical Research
Volume	42
Issue number	4
DOIs	https://doi.org/10.1080/10715760801975735
Publication status	Published - 2008 Sep 4
Externally published	Yes

Keywords

AP-1
Arsenite
Genistein
Heme oxygenase-1
JNK
Nrf2
PD153035
Src

ASJC Scopus subject areas

Biochemistry

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Differential roles for Nrf2 and AP-1 in upregulation of HO-1 expression by arsenite in murine embryonic fibroblasts. / Harada, Harumi; Sugimoto, Rika; Watanabe, Ayaka; Taketani, Shigeru; Okada, Kosuke; Warabi, Eiji; Siow, Richard; Itoh, Ken; Yamamoto, Masayuki; Ishii, Tetsuro.

In: Free Radical Research, Vol. 42, No. 4, 04.09.2008, p. 297-304.

Research output: Contribution to journal › Article › peer-review

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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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