title: MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling.
abstract: Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes. Contrarily, Nrf2 knockdown or S40T mutation almost nullified MHY1485-induced cytoprotection. MHY1485 suppressed UV-induced reactive oxygen species production and DNA single strand breaks in skin keratinocytes and fibroblasts. Together, we conclude that MHY1485 inhibits UV-induced skin cell damages via activating mTOR-Nrf2 signaling.
authors.affiliation: Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Qiu-Yun
authors.initials: QY
authors.lastname: Xu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Guo
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Jin-Wen
authors.initials: JW
authors.lastname: Huang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming, China.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Bi
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002478:Cells, Cultured; D019610:Cytoprotection; D053904:DNA Breaks, Single-Stranded; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009025:Morpholines / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: C577756:4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine; D009025:Morpholines; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D014227:Triazines; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: MHY1485; Nrf2; mTOR; skin cell damage; ultra violet (UV)