期刊
PHARMACOLOGICAL RESEARCH
卷 63, 期 3, 页码 233-240出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2010.11.005
关键词
Antioxidant response element (ARE); Nrf2; ERK; Allyl isothiocyanate; Butyl isothiocyanate; Phenylethyl isothiocyanate
资金
- DFG Cluster of Excellence
- BMBF [FKZ 0315397]
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 ally! 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,gamma-glutamyl cysteine synthetase (gamma GCS), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1). HO-1 and gamma GCS 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. (C) 2010 Elsevier Ltd. All rights reserved.
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