title: Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response: a possible mechanism for melanocyte degeneration in vitiligo.
abstract: Vitiligo melanocytes possess higher susceptibility to oxidative insults. Consistent with this, impairment of the antioxidant defense system has been reported to be involved in the onset and progression of vitiligo. Our previous study showed that the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and its downstream antioxidant enzyme heme oxygenase-1 (HO-1) are crucial for melanocytes to cope with H2O2-induced oxidative damage. Here, we sought to determine whether the diminished Nrf2-ARE activity that contributes to reduced downstream antioxidant enzymes and increased oxidative stress could be the reason why melanocytes are more vulnerable to vitiligo. We found that vitiligo melanocytes exhibited hypersensitivity to H2O2-induced oxidative injury because of reduced Nrf2 nuclear translocation and transcriptional activity, which led to decreased HO-1 expression and aberrant redox balance. Moreover, we also found that the level of serum HO-1 was significantly decreased and that of IL-2 was markedly increased in 113 vitiligo patients when compared with healthy controls. These data demonstrate that impaired activation of Nrf2 under oxidative stress could result in decreased expression of antioxidant enzymes and increased death of vitiligo melanocytes.
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jian
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Cui
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Bangmin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: lichying@fmmu.edu.cn.
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: gaotw75401@hotmail.com.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D061745:Antioxidant Response Elements / Q000502:physiology*; D002374:Catalase / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D051547:Heme Oxygenase-1 / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008544:Melanocytes / Q000378:metabolism*; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000032:analysis; D014820:Vitiligo / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D006861:Hydrogen Peroxide; D002374:Catalase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase