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

被引：41

作者：

Harada, Harumi ^{[1
]}

Sugimoto, Rika ^{[1
]}

Watanabe, Ayaka ^{[1
]}

Taketani, Shigeru ^{[2
]}

Okada, Kosuke ^{[1
]}

Warabi, Eiji ^{[1
]}

Siow, Richard ^{[3
]}

Itoh, Ken ^{[4
]}

Yamamoto, Masayuki ^{[1
]}

Ishii, Tetsuro ^{[1
]}

机构：

[1] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan

[2] Kyoto Inst Technol, Dept Biotechnol, Kyoto 606, Japan

[3] Kings Coll London, Sch Med, Div Cardiovasc, London SE1 1UL, England

[4] Hirosaki Univ, Ctr Adv Med Res, Sch Med, Aomori, Japan

来源：

FREE RADICAL RESEARCH | 2008年 / 42卷 / 04期

关键词：

heme oxygenase-1; Nrf2; AP-1; JNK; src; genistein; PD153035; arsenite;

D O I：

10.1080/10715760801975735

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：297 / 304

页数：8

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