Cell Stress and Chaperones

, Volume 20, Issue 5, pp 805–810 | Cite as

SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3

  • Yongfeng Wang
  • Yuanbin Zhu
  • Shigang Xing
  • Ping Ma
  • Dianjie Lin
Original Paper


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.


Chronic obstructive pulmonary disease Cigarette smoking SIRT5 FOXO3 Apoptosis 


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Copyright information

© Cell Stress Society International 2015

Authors and Affiliations

  • Yongfeng Wang
    • 1
    • 2
  • Yuanbin Zhu
    • 2
  • Shigang Xing
    • 2
  • Ping Ma
    • 2
  • Dianjie Lin
    • 1
    • 3
  1. 1.School of MedicineShandong UniversityJi’nanPeople’s Republic of China
  2. 2.Department of Respiratory MedicineYishui Central HospitalLinyiPeople’s Republic of China
  3. 3.Department of Respiratory MedicineShandong Provincial HospitalJinanPeople’s Republic of China

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