title: The effect of resveratrol and its methylthio-derivatives on the Nrf2-ARE pathway in mouse epidermis and HaCaT keratinocytes.
abstract: Resveratrol is the most extensively studied stilbene derivative. We previously showed that methylthiostilbenes were more effective inhibitors of CYP1A1 and 1B1 activity than resveratrol. In this study, we investigated whether resveratrol and its methylthio-substituted derivatives, i.e. 3-M-4'-MTS (S2), 3,5-DM-4'-MTS (S5) and 3,4,5-TM-4'-MTS (S7) could activate Nrf2 signaling in the mouse epidermis and in human keratinocytes. Western blot analysis showed translocation of Nrf2 from the cytosol to the nucleus in both models. All of the tested stilbenes increased GST activity, but resveratrol was the most effective inducer. Moreover, only resveratrol increased the protein level of GSTP in the mouse epidermis. GSTM was enhanced in HaCaT cells after the treatment with derivatives S2 and S5. The same effect was observed for GSTP in the case of compound S2. Resveratrol and its derivatives reduced the NQO2 protein level in HaCaT cells. Thus, it is possible that increased expression of GSTP or GSTM and GST activity was linked with NQO2 inhibition in these cells. The results of this study indicate that resveratrol and its methylthioderivatives activate Nrf2 not only in the mouse epidermis, but also in human keratinocytes. Upregulating GST isozymes might be particularly important for deactivating chemical carcinogens, such as PAH.
authors.affiliation: Department of Pharmaceutical Biochemistry, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Violetta
authors.initials: V
authors.lastname: Krajka-Kuźniak
authors.forename: Hanna
authors.initials: H
authors.lastname: Szaefer
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stefański
authors.forename: Stanisław
authors.initials: S
authors.lastname: Sobiak
authors.forename: Michał
authors.initials: M
authors.lastname: Cichocki
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011808:Quinone Reductases / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D013267:Stilbenes; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D005982:Glutathione Transferase; D000077185:Resveratrol