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

Free Radical Research
Harumi HaradaTetsuro Ishii

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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Citations

Mar 13, 2009·The Journal of Biological Chemistry·Alejo A MoralesLawrence H Boise
May 8, 2010·Antioxidants & Redox Signaling·John D HayesAlbena T Dinkova-Kostova
Jan 20, 2010·Toxicology and Applied Pharmacology·Dan MengXianglin Shi
Sep 1, 2009·Toxicology and Applied Pharmacology·Qiang ZhangMelvin E Andersen
Apr 18, 2014·Annals of Clinical and Translational Neurology·Che-Feng ChangJian Wang
Apr 24, 2014·Biochemical and Biophysical Research Communications·Jin-Sun Park, Hee-Sun Kim
Jan 12, 2010·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Julia L ZhongRex M Tyrrell
Apr 8, 2010·Free Radical Research·Ioanna-Katerina AggeliCatherine Gaitanaki
Jan 13, 2017·Journal of Animal Science and Biotechnology·Shoulong DengZhengxing Lian

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