Role of reciprocal interaction between autophagy and endoplasmic reticulum stress in apoptosis of human bronchial epithelial cells induced by cigarette smoke extract
Role of reciprocal interaction between autophagy and endoplasmic reticulum stress in apoptosis of human bronchial epithelial cells induced by cigarette smoke extract
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DOI：
10.1002/iub.1937
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发表时间：
2019-01-01
期刊：
影响因子：
4.6
通讯作者：
Liu, Zhaoqian
中科院分区：
文献类型：
--
作者：
He, Baimei;Chen, Qiong;Liu, Zhaoqian
内质网应激(ERS)诱导的气道上皮细胞凋亡在慢性阻塞性肺疾病(COPD)的发病机制中起重要作用。此外，自噬与细胞凋亡下的ERS密切相关。本研究旨在探讨自噬和ERS之间的相互作用在香烟烟雾提取物(CSE)诱导人支气管上皮细胞(HBE)凋亡中的作用。流式细胞仪检测细胞凋亡率。Western印迹法检测蛋白表达。用实时定量逆转录聚合酶链式反应(qRT-PCR)检测基因表达。结果表明，CSE可诱导HBE细胞凋亡、自噬和ERS相关蛋白的表达。此外，3-MA抑制自噬显著降低GRP78、p-PERK和p-eIF2α的蛋白表达，增加CHOP、ATF4和caspase-4的表达，而4-PBA抑制ERS则导致自噬抑制。此外，CSE诱导的自噬作用可被GRP78、PERK或eIF2α基因敲除减弱，但可被ATF4或CHOP基因敲除增强，而CSE诱导的HBE凋亡可被GRP78、PERK或eIF2α基因敲除增强，但可被ATF4或CHOP基因敲除减弱。此外，NaHS和褪黑素均通过SIRT1/ORP150途径抑制CSE诱导的细胞凋亡，增强CSE诱导的自噬，增加GRP78、p-PERK和p-eIF2α，降低CHOP、ATF4和caspase-4。总之，这项研究为自噬和ERS之间的相互作用在CSE诱导HBE细胞凋亡中的作用提供了证据。(C)2018年IUBMB Life，71(1)：66-80,2019年
Endoplasmic reticulum stress (ERS)-induced apoptosis of airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Furthermore, autophagy is closely related to ERS under apoptosis. Here, this study aimed to investigate the role of the reciprocal interaction between autophagy and ERS in the cigarette smoke extract (CSE)-induced apoptosis of human bronchial epithelial (HBE) cells. Cell apoptosis was detected by flow cytometry analysis. Protein expression was examined by Western blot. The mRNA expression was detected using real-time quantitative reverse transcription PCR (qRT-PCR). The results showed that CSE treatment induced apoptosis, autophagy, and expression of ERS-related proteins in HBE cells. Furthermore, autophagy inhibition by 3-MA significantly decreased protein expression of GRP78, p-PERK, and p-eIF2 alpha and increased CHOP, ATF4, and caspase-4, whereas ERS inhibition by 4-PBA led to autophagy suppression. Moreover, the CSE-induced autophagy was diminished by knockdown of GRP78, PERK, or eIF2 alpha but enhanced by knockdown of ATF4 or CHOP; however, the CSE-induced HBE apoptosis was enhanced by knockdown of GRP78, PERK, or eIF2 alpha but was attenuated by knockdown of ATF4 or CHOP. Additionally, both sodium hydrosulfide (NaHS) and melatonin attenuated the CSE-induced apoptosis, enhanced the CSE-induced autophagy, increased GRP78, p-PERK, and p-eIF2 alpha, and decreased CHOP, ATF4, and caspase-4, via SIRT1/ORP150 pathway. Collectively, this study provided evidence about the role of the reciprocal interaction between autophagy and ERS in CSE-induced apoptosis of HBE cells. (c) 2018 IUBMB Life, 71(1):66-80, 2019