Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture.
Nrf2 is a basic leucine zipper transcriptional activator essential for the coordinated transcriptional induction of phase-2 and antioxidant enzymes. Brassica vegetables contain phytochemicals including glucoraphanin, the precursor of sulforaphane (SFN) and glucobrassicin, the precursor of indole-3-carbinole (I3C) and ascorbigen (ABG). The degradation products SFN, I3C and ABG may be capable of inducing cytoprotective genes in skin. In this study, we tested the potency of SFN, ABG and I3C in affecting Nrf2-dependent gene expression in human keratinocytes in culture. SFN but not ABG and its precursors I3C and ascorbic acid induced Nrf2 dependent gene expression at a relatively low concentration (5 micromol/l). Induction of Nrf2 due to SFN was accompanied by an increase in mRNA and protein levels of NADPH quinone oxidoreductase 1, heme oxygenase 1 and gamma-glutamylcysteine-synthetase. Furthermore, SFN elevated cellular glutathione levels and antagonized tumor necrosis factor-alpha-induced NFkappaB transactivation. Therefore, SFN treatment may present a strategy for enhancing the cellular defense mechanisms in skin.
Wagner
Anika E
AE
Institute of Human Nutrition and Food Science, Christian-Albrechts-University, Kiel, Germany.
Ernst
Insa
I
Iori
Renato
R
Desel
Christine
C
Rimbach
Gerald
G
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D017879:Isothiocyanates; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D007211:Indoles; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; C053152:ascorbigen; C016517:indole-3-carbinol; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005721:Glutamate-Cysteine Ligase; C016766:sulforaphane; D005978:Glutathione; D001205:Ascorbic Acid