Protective effect of autophagy on endoplasmic reticulum stress induced apoptosis of alveolar epithelial cells in rat models of COPD.

Yao Tang,Shao-Hua Fan,Qi-Hang Cai,Zi-Feng Zhang,Yong-Jian Wang,Meng-Qi Xiao,Jun Lu,Yuan-Lin Zheng,Jin-Yu Zhu,Dong-Mei Wu,Qi Hang Cai ,Zi Feng Zhang ,Dong Mei Wu

doi:10.1042/bsr20170803

Abstract

During the present study, we explored the protective effects of autophagy on endoplasmic reticulum (ER) stress (ERS) induced apoptosis belonging to alveolar epithelial cells (AECs) in rat models with chronic obstructive pulmonary disease (COPD). Fifty-six 12-week-old male Sprague–Dawley (SD) rats were randomly assigned into the COPD group (rats exposed to cigarette smoke (CS)), the 3-methyladenine (3-MA) intervention group (COPD rats were administrated with 10 mg/kg autophagy inhibitors), the chloroquine (CQ)-intervention group (COPD rats were administrated 40 mg/kg CQ), and the control group (rats breathed in normal saline). The forced expiratory volume in 0.3 s/forced vital capacity (FEV0.3/FVC%), inspiratory resistance (RI), and dynamic lung compliance (Cdyn) were measured and recorded. The expressions of PKR-like ER kinase (PERK) and CCAAT/enhancer-binding protein-homologous protein (CHOP) were detected by immunohistochemistry. The cell apoptotic rates of AECs were analyzed by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end-labeling (TUNEL) staining. The expression levels of light chain 3 (LC3-II), p62, Beclin-1, ATG5, ATG7, Caspase-12, and Caspase-3 were detected by Western blotting. Results showed that the COPD group exhibited a lower FEV0.3/FVC% and Cdyn, and a higher RI than the control group. Compared with the control group, the integrated optical density (IOD) values of PERK and CHOP, the apoptotic rate of AECs, and expressions of LC3-II, Beclin-1, ATG5, ATG7, Caspase-3, and Caspase-12 expressions were significantly higher, whereas p62 expression was significantly lower in the COPD group. Based on the results obtained during the present study, it became clear that the inhibition of autophagy could attenuate the ERS-induced apoptosis of AECs in rats with COPD.

Highlights

Chronic obstructive pulmonary disease (COPD) is a term used to describe a group of diseases that previously included bronchitis and emphysema [1]
We investigated how the apoptosis of alveolar epithelial cell (AEC) induced by ERS in COPD rats as well as the protective effects of autophagy, can prove that the inhibition of autophagy itself might alleviate ERS-induced apoptosis of AECs in rat models of COPD
Our study demonstrated that both 3-MA and CQ are beneficial in inhibiting the process of autophagy. 3-MA belongs to a group of phosphoinositide-3-kinase (PI3K) inhibitors, which have been widely used as autophagy inhibitors based on their inhibitory effects on class 3 PI3K activity, an essential component for the induction of autophagy [23]

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a term used to describe a group of diseases that previously included bronchitis and emphysema [1]. COPR is characterized as a progressive disease that generally manifests itself with persistent airflow limitation and enhanced chronic inflammatory response in the lung tissues [2]. The global initiative for COPD (GOLD) has defined COPD as “a common preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. COPD is more common in the c 2017 The Author(s).

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