title: Redox regulation of SIRT1 in inflammation and cellular senescence.
abstract: Sirtuin 1 (SIRT1) regulates inflammation, aging (life span and health span), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging, in which oxidative stress occurs. SIRT1 is regulated by a NAD(+)-dependent DNA repair enzyme, poly(ADP-ribose) polymerase-1 (PARP1), and subsequent NAD(+) depletion by oxidative stress may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to posttranslational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65, and FOXO3, thereby enhancing the inflammatory, prosenescent, and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1 and its roles in PARP1 and NF-κB activation, and FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging, are discussed. Furthermore, we have also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases.
authors.affiliation: Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Jae-woong
authors.initials: JW
authors.lastname: Hwang
authors.affiliation: Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yao
authors.affiliation: Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Caito
authors.affiliation: Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Isaac K
authors.initials: IK
authors.lastname: Sundar
authors.affiliation: Lung Biology and Disease Program, Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: irfan_rahman@urmc.rochester.edu.
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D016922:Cellular Senescence; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000502:physiology*; D051996:Transcription Factor RelA / Q000502:physiology
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D006657:Histones; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D052250:Nitric Oxide Synthase Type III; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: COPD; FOXO3; Free radicals; GSH; Inflammation; NF-κB; Oxidants; Redox signaling; SIRT1; Senescence; Tobacco smoke
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