title: Heme oxygenase-1 protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway.
abstract: Oxidative stress caused by hydrogen peroxide (H(2)O(2)) leads to cell death and has been implicated in the pathogenesis of vitiligo. The nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE), a major antioxidant pathway, regulates oxidative stress-related cytoprotective genes. We hypothesized that the Nrf2-ARE pathway protects human melanocytes from H(2)O(2)-induced oxidative damage through the induction of downstream antioxidative genes. Thus, we used Nrf2 short interfering RNA (siRNA) and pCMV6-XL5-Nrf2 to downregulate or upregulate Nrf2 expression in immortalized human melanocyte cell line PIG1. The melanocytes were then analyzed under different oxidative stress conditions for cell viability and apoptosis. Our study demonstrated that heme oxygenase-1 (HO-1) was the most induced antioxidant gene in PIG1 cells after treatment with H(2)O(2). Knockdown of Nrf2 or zinc protoporphyrin IX (ZnPP) treatment increased cell death caused by H(2)O(2) in melanocytes, but upregulation of Nrf2 or hemin treatment reduced cell death caused by H(2)O(2) in melanocytes. In addition, the H(2)O(2)-induced Nrf2-ARE/HO-1 pathway was confirmed in primary cultured human melanocytes by examining the expression and translocation of Nrf2 and HO-1. These data suggested that regulation of the Nrf2/HO-1 pathway can reduce H(2)O(2)-induced oxidative damage in human melanocytes. Our data demonstrate that HO-1 protects human melanocytes from oxidative damage via the Nrf2-ARE pathway.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jian
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018384:Oxidative Stress; D020218:Response Elements / Q000502:physiology*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1