Sirtuin 3 Inhibits Airway Epithelial Mitochondrial Oxidative Stress in Cigarette Smoke-Induced COPD.

Ming Zhang,Jie Zhang,Michael Roth,Rong Shi,Yali Li,Xia Yang,Li Zhang,Yeli Zhang

doi:10.1155/2020/7582980

Abstract

Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown. The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD. Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats. Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats. In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner. Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE. In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells. These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible and progressive airflow limitation
Sirtuin 3 (Sirt3) protein expression in the airway epithelium was determined by immunohistochemistry, and the results revealed that its expression in airway epithelial cells was significantly decreased in COPD rats compared to the control group (Figure 1(f))
The presented data demonstrate that the protein expression of Sirt3 in the airway epithelium of COPD rats was significantly decreased and was associated with severe mitochondrial damage

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible and progressive airflow limitation. Cigarette smoking is assumed to be the main cause of COPD, but the etiology and pathogenesis of this disease are still unclear [4]. Alterations of the airway epithelium function have been proposed to play an important role in the pathogenesis of chronic airway inflammatory disease, including COPD [5]. In this regard, cigarette smoke-induced oxidative stress of the airway epithelium is implicated to initiate the pathogenesis in COPD [6]. Mitochondrial oxidative stress of the airway epithelium appears to be a cause rather than a consequence of COPD [7]

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