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- Title
Melanocyte-protective effect of afzelin is mediated by the Nrf2- ARE signalling pathway via GSK-3β inactivation.
- Authors
Jung, Eunsun; Kim, Jin Hee; Kim, Mi Ok; Lee, Sang Yeol; Lee, Jongsung
- 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-si RNA expression. Furthermore, we found that the expression of Nrf2-si RNA 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.
- Subjects
VITILIGO; FLAVONOL glycosides; OXIDATIVE stress; MAMMAL physiology; MELANOCYTES; GLYCOGEN synthase kinase-3; THERAPEUTICS
- Publication
Experimental Dermatology, 2017, Vol 26, Issue 9, p764
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.13277