AUTHOR=Lin Fan , Liao Chengcheng , Sun Yun , Zhang Jinsheng , Lu Weiwei , Bai Yu , Liao Yixuan , Li Minxia , Ni Xianqiang , Hou Yuelong , Qi Yongfen , Chen Yahong 

TITLE=Hydrogen Sulfide Inhibits Cigarette Smoke-Induced Endoplasmic Reticulum Stress and Apoptosis in Bronchial Epithelial Cells

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00675

DOI=10.3389/fphar.2017.00675

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Apoptosis of lung structural cells contributes to the process of lung damage and remodeling in chronic obstructive pulmonary disease (COPD). Our previous studies demonstrated that exogenous hydrogen sulfide (H<sub>2</sub>S) can reduce the lung tissue pathology score, anti-inflammation and anti-oxidation effects in COPD, but the effect of H<sub>2</sub>S in regulating cigarette smoke (CS) induced bronchial epithelial cell apoptosis and the underlying mechanisms are not clear.</p><p><bold>Objectives:</bold> To investigate the effect of H<sub>2</sub>S on CS induced endoplasmic reticulum stress (ERS) and bronchial epithelial cell apoptosis.</p><p><bold>Methods:</bold> Male Sprague–Dawley rats randomly divided into four groups for treatment: control, CS, NaHS + CS, and propargylglycine (PPG) + CS. The rats in the CS group were exposed to CS generated from 20 commercial unfiltered cigarettes for 4 h/day, 7 days/week for 4 months. Since the beginning of the third month, freshly prepared NaHS (14 μmol/kg) and PPG (37.5 mg/kg) were intraperitoneally administered 30 min before CS-exposure in the NaHS and PPG groups. 16HBE cells were pretreated with Taurine (10 mM), 5 mmol/L 4-phenylbutyric acid (4-PBA) or NaHS (100, 200, and 400 μM) for 30 min, and then cells were exposed to 40 μmol/L nicotine for 72 h. ERS markers (GRP94, GRP78) and ERS-mediated apoptosis markers 4-C/EBP homologous protein (CHOP), caspase-3 and caspase-12 were assessed in rat lung tissues and human bronchial epithelial cells. The apoptotic bronchial epithelial cells were detected by Hoechst staining <italic>in vitro</italic> and TUNEL staining <italic>in vivo</italic>.</p><p><bold>Results:</bold> In CS exposed rats, peritoneal injection of NaHS significantly inhibited CS induced overexpression ERS-mediated apoptosis markers and upregulation of apoptotic rate in rat lungs, and inhibiting the endogenous H2S production by peritoneal injection of PPG exacerbated these effects. In the nicotine-exposed bronchial epithelial cells, appropriate concentration of NaHS and ERS inhibitors taurine and 4-PBA inhibited nicotine-induced upregulation of apoptotic rate and overexpression of ERS-mediated apoptosis markers.</p><p><bold>Conclusion:</bold> H<sub>2</sub>S inhibited lung tissue damage by attenuating CS induced ERS in rat lung and exogenous H<sub>2</sub>S attenuated nicotine induced ERS-mediated apoptosis in bronchial epithelial cells.</p>