title: SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3.
abstract: Cigarette smoking plays an important role in increased incidence of chronic obstructive pulmonary disease (COPD). The underlying mechanism in which cigarette smoking induced impairment of lung epithelial cells is still unknown. SIRT5 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, which has been implicated in the regulation of metabolism, stress responses, and aging. Forkhead box O3 (FOXO3) belongs to the O subclass of the forkhead family of transcription factors. It is also involved in protection from oxidative stress by upregulating antioxidants in epithelial cells. Here, we show that cigarette smoke extract (CSE) induces SIRT5 to deacetylate FOXO3 at K271 and K290. Deacetylation of FOXO3 promotes its nuclear localization. Notably, transfection with FOXO3 K271R- or K290R-attenuated CSE-induced apoptosis in SIRT5 knocked down cells, suggesting the protective effects of SIRT5, is mediated by FOXO3. In contrast, CSE stress upregulates SIRT5, which activates FOXO3α leading to rescuing apoptosis. Thus, SIRT5 constitutes a determinant of apoptosis by CSE in lung epithelial cells.
authors.affiliation: School of Medicine, Shandong University, No.44, Wenhua West Road, Lixia District, Ji'nan, Shandong Province, 250012, People's Republic of China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Shigang
authors.initials: S
authors.lastname: Xing
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Dianjie
authors.initials: D
authors.lastname: Lin
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D011650:Pulmonary Alveoli / Q000166:cytology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D037761:Sirtuins / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C508544:SIRT5 protein, human; D037761:Sirtuins