Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts.
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)H:quinone 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.
Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany.
Insa M A
IM
Ernst
Anika E
AE
Wagner
Christine
C
Schuemann
Niels
N
Storm
Wolfgang
W
Höppner
Frank
F
Döring
Achim
A
Stocker
Gerald
G
Rimbach
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D041681:NIH 3T3 Cells
D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C039156:butyl isothiocyanate; C058305:phenethyl isothiocyanate; C004471:allyl isothiocyanate