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 |
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Pages (from-to) | 297-304 |
Number of pages | 8 |
Journal | Free Radical Research |
Volume | 42 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2008 |
Externally published | Yes |
Keywords
- AP-1
- Arsenite
- Genistein
- Heme oxygenase-1
- JNK
- Nrf2
- PD153035
- Src
ASJC Scopus subject areas
- Biochemistry