Redox regulation of SIRT1 in inflammation and cellular senescence

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...

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Veröffentlicht in:Free radical biology & medicine 2013-08, Vol.61, p.95-110
Hauptverfasser: Hwang, Jae-woong, Yao, Hongwei, Caito, Samuel, Sundar, Isaac K., Rahman, Irfan
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •SIRT1 regulates inflammaging and cellular senescence.•SIRT1 is a redox-sensitive protein that undergoes posttranslational modifications.•SIRT1 is regulated by PARP1 in response to redox changes and oxidative stress.•SIRT1 regulates RelA/p65, p53, and FOXO3-mediated inflammation and senescence.•Activation of SIRT1 attenuates inflammaging in chronic inflammatory diseases.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2013.03.015