Research Paper Volume 11, Issue 24 pp 11844—11864
Hydrogen sulfide attenuates mitochondrial dysfunction-induced cellular senescence and apoptosis in alveolar epithelial cells by upregulating sirtuin 1
- 1 State Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- 2 Key Laboratory of National Health Commission for the Diagnosis and Treatment of COPD, Departments of Respiratory and Critical Diseases, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China
received: May 19, 2019 ; accepted: November 7, 2019 ; published: December 23, 2019 ;https://doi.org/10.18632/aging.102454
How to Cite
Copyright © 2019 Guan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Hydrogen sulfide (H2S), an endogenous gaseous signal molecule, regulates many pathologies related to aging. Sirtuin 1 (SIRT1) has been shown to protect against mitochondrial dysfunction and other pathological processes, including premature senescence. This study was aimed to investigate whether and how H2S attenuates senescence and apoptosis of alveolar epithelial cells via a SIRT1-dependent mechanism. Our results showed that treatment with sodium hydrosulfide (NaHS), a donor of H2S, attenuated cigarette smoke extract (CSE)-induced oxidative stress, mitochondrial dysfunction, cellular senescence and apoptosis in A549 cells. This was associated with SIRT1 upregulation. SIRT1 activation by a pharmacological activator, SRT1720, attenuated CSE-induced oxidative stress and mitochondrial dysfunction in A549 cells. While SIRT1 inhibition by EX 527 or silencing by siRNA transfection significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress, mitochondrial dysfunction and the imbalance of mitochondrial fusion and fission. Also, SIRT1 inhibition or silencing abolished the protection of NaHS against CSE-induced cellular senescence and apoptosis. In conclusion, H2S attenuates CSE-induced cellular senescence and apoptosis by improving mitochondrial function and reducing oxidative stress in alveolar epithelial cells in a SIRT1-dependent manner. These findings provide novel mechanisms underlying the protection of H2S against cigarette smoke-induced COPD.
AECs: alveolar epithelial cells; COPD: chronic obstructive pulmonary disease; CSE: cigarette smoke extract; FIS1: mitochondrial fission 1 protein; FOXO3: forkhead box O3; MFN1: mitofusin 1; MPST: 3-mercaptypyruvate sulfurtransferase; mtDNA: mitochondrial DNA; mtROS: mitochondrial ROS; H2S: hydrogen sulfide; ROS: reactive oxygen species; SA–β-gal: senescence-associated β-gal; SASP: senescence-associated secretory phenotype; SIRT1: Sirtuin 1; OCR: oxygen consumption rate; OPA1: opticatrophy 1; Δψm: mitochondrial membrane potential.