Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts.
Pharmacol Res
; 63(3): 233-40, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-21109004
ABSTRACT
The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and in vivo via a Nrf2 dependent signal transduction pathway. However, little is known regarding the effect of structurally related compounds such as allyl isothiocyanate (AITC), butyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) on Nrf2 target gene expression. In this study AITC, BITC and PEITC significantly increased phosphorylation of ERK1/2, an upstream target of Nrf2 in NIH3T3 fibroblasts. EKR1/2 phosphorylation was accompanied by an increased nuclear translocation and transactivation of Nrf2. AITC, BITC and PEITC significantly enhanced mRNA and protein levels of the Nrf2 targets γ-glutamyl cysteine synthetase (γGCS), heme oxygenase-1 (HO-1) and NAD(P)Hquinone oxidoreductase (NQO1). HO-1 and γGCS both contain CpG islands within their promoter region. However, analysis of DNA methylation status in NIH3T3 cells indicated that expression of these genes may not be dependant on promoter methylation. Current data indicate that not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isotiocianatos
/
Fator 2 Relacionado a NF-E2
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Fibroblastos
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha