title: Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo.
abstract: In vitiligo, melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis and to the genetic antioxidant defects. Autophagy is a controlled self-digestion process which can protect cells against oxidative damage. However, the exact role of autophagy in vitiligo melanocytes in response to oxidative stress and the mechanism involved are still not clear. To determine the implications of autophagy for melanocyte survival in response to oxidative stress, we first detected the autophagic flux in normal melanocytes exposure to H2O2, and found that autophagy was significantly enhanced in normal melanocytes, for protecting cells against H2O2-induced oxidative damage. Nevertheless, vitiligo melanocytes exhibited dysregulated autophagy and hypersensitivity to H2O2-induced oxidative injury. In addition, we confirmed that the impairment of Nrf2-p62 pathway is responsible for the defects of autophagy in vitiligo melanocytes. Noteworthily, upregulation of the Nrf2-p62 pathway or p62 reduced H2O2-induced oxidative damage of vitiligo melanocytes. Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo. Upregulation of p62-dependent autophagy may be applied to vitiligo treatment in the future.
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yuanmin
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Weigang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Cui
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000071456:Sequestosome-1 Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014820:Vitiligo / Q000473:pathology*
chemical_list: D051267:NF-E2-Related Factor 2; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D006861:Hydrogen Peroxide