title: Melanocyte-protective effect of afzelin is mediated by the Nrf2-ARE signalling pathway via GSK-3β inactivation.
abstract: Vitiligo is an acquired condition characterized by depigmented, cutaneous lesions that result from the death of pigment-producing cells, melanocytes. The occurrence of oxidative stress has been proposed as a pathogenetic mechanism for melanocyte degeneration in vitiligo. Therefore, in this study, we investigated the cytoprotective effects of afzelin against oxidative stress and its mechanism of action in human epidermal melanocytes. We found that afzelin significantly inhibited hydrogen peroxide-induced cell death, cellular reactive oxygen species production and lipid peroxidation in melanocytes. In an antioxidant response element (ARE)-luciferase reporter assay, afzelin increased ARE-luciferase reporter activity in a concentration-dependent manner. Consistently, the expression of antioxidant genes, including NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1) and catalase, was enhanced by afzelin treatment. Nuclear translocation of Nrf2 also increased in response to afzelin treatment. In addition, the phosphorylation of glycogen synthase kinase-3β (GSK-3β) was induced by afzelin treatment. The enhancement of HO-1 gene expression by afzelin treatment was reduced by Nrf2-siRNA expression. Furthermore, we found that the expression of Nrf2-siRNA significantly attenuated the cytoprotective effect of afzelin against hydrogen peroxide. These data suggest that the cytoprotective effects of afzelin against hydrogen peroxide may be mediated by Nrf2-ARE signalling via GSK-3β inactivation. Our data suggest the novel use of afzelin for the prevention of oxidative stress-induced damage in melanocytes and its potential as a therapeutic agent for vitiligo.
authors.affiliation: Biospectrum Life Science Institute, Seongnam City, Gyunggi Do, Korea.
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.affiliation: College of Herbal Bio-Industry, Daegu Haany University, Gyeongsan City, Gyeongsangbuk Do, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, Gyunggi Do, Korea.
authors.forename: Mi Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: Department of Life Science, Gachon University, Seongnam-Si, Gyunggi Do, Korea.
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, Gyunggi Do, Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
mesh_terms: D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D015227:Lipid Peroxidation / Q000187:drug effects; D008362:Mannosides / Q000494:pharmacology / Q000627:therapeutic use*; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D014820:Vitiligo / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D008362:Mannosides; D008543:Melanins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D044945:Proanthocyanidins; C477954:afzelin; D006861:Hydrogen Peroxide; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: GSK-3β; Nrf2; afzelin; cytoprotection; oxidative stress