title: Cigarette smoke extract induces the expression of GRP78 in A549 cells via the p38/MAPK pathway.
abstract: Apoptosis of alveolar epithelial cells has been implicated in the pathogenesis of chronic obstructive pulmonary disease. To determine the involvement of glucose‑regulated protein 78 (GRP78) in the cigarette smoke extract (CSE)‑induced apoptosis of alveolar epithelial cells and the potential mechanisms underlying this effect, A549 cells that originate from alveolar type II epithelial cells were exposed to various CSE conditions in the present study. GRP78 expression and its effect on the apoptosis of A549 cells were investigated using techniques such as RT-PCR, western blot analysis, gene knockdown by GRP78 siRNA interference and the terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. The activity of the p38/mitogen‑activated protein kinase (MAPK) pathway and its involvement in GRP78 expression were also analyzed using SB203580, a p38/MAPK pathway inhibitor. It was demonstrated that GRP78 expression in the cells was significantly upregulated following CSE exposure and a 12‑h exposure of 5% CSE was the most efficient in inducing GRP78 expression. This CSE‑induced GRP78 expression was significantly attenuated by GRP78 siRNA or by the use of SB203580. The downregulation of GRP78 expression by GRP78 siRNA also led to the increased expression of caspase-3 and an increased apoptotic index (AI, P<0.05 vs. other groups). These results suggested that CSE induced GRP78 expression in A549 cells. This study demonstrated that upregulated GRP78 expression may be anti‑apoptotic effects and the p38/MAPK pathway was involved in the process of CSE‑induced GRP78 expression in A549 cells.
authors.affiliation: Department of Geriatric Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Baimei
authors.initials: B
authors.lastname: He
authors.forename: Bailing
authors.initials: B
authors.lastname: Luo
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.forename: Lemeng
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012907:Smoking / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases
keywords: cigarette smoke extract; A549 cells; alveolar epithelial cells; glucose-regulated protein 78; apoptosis