Differential roles for Nrf2 and AP-1 in upregulation of HO-1 expression by arsenite in murine embryonic fibroblasts.
Free Radic Res
; 42(4): 297-304, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18404528
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Enzimológica da Expressão Gênica
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Fator de Transcrição AP-1
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Heme Oxigenase-1
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Fator 2 Relacionado a NF-E2
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Fibroblastos
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article