title: Molecular Insights into SIRT1 Protection Against UVB-Induced Skin Fibroblast Senescence by Suppression of Oxidative Stress and p53 Acetylation.
abstract: Stresses, such as exposure to ultraviolet radiation and those associated with aging, are known to cause premature cellular senescence that is characterized by growth arrest and morphological and gene expression changes. This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence. Under in vitro experimental conditions, exposure to a subcytotoxic dose of UVB enhanced human skin fibroblasts senescence, as characterized by increased β-galactosidase activity and increased levels of senescence-associated proteins. However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration. Exposure to UVB-induced cell senescence was associated with oxidative stress and p38 mitogen-activated protein kinase activation. Molecular analysis demonstrated that deacetylation of Forkhead box O3α (FOXO3α) by SIRT1 changed the transcriptional activity of FOXO3α and increased resistance to the oxidative stress. In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB. Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB. The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging.
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Byung Hyun
authors.initials: BH
authors.lastname: Park
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, Texas.
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea. hyjung@pusan.ac.kr.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000528:radiation effects*; D005347:Fibroblasts / Q000528:radiation effects; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000502:physiology; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress; D056564:Sirtuin 1 / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: FOXO3α; SIRT1; Senescence; UVB; p53