title: Cigarette smoke induces endoplasmic reticulum stress response and proteasomal dysfunction in human alveolar epithelial cells.
abstract: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease. Cigarette smoke (CS) causes oxidative stress and severe damage to proteins in the lungs. One of the main systems to protect cells from the accumulation of damaged proteins is the ubiquitin-proteasome pathway. In the present study, we aimed to find out whether exposure of alveolar epithelial cells to CS induces an endoplasmic reticulum (ER) stress response by accumulation of damaged proteins that are inefficiently degraded by the proteasomes. The hypothesis was tested in a human alveolar epithelial cell line (A549) exposed to gas-phase CS. Exposure to gas-phase CS for 5 min caused an increase in the amount of ubiquitin-protein conjugates within 4 h. Cigarette smoke exposure also induced the ER stress response marker eIF2α, followed by a significant reduction of nascent protein synthesis and increase in the level of free intracellular amino acids. Moreover, CS exposure significantly reduced all three proteasomal activities (caspase-, trypsin- and chymotrypsin-like activity) within 4 h, which was still present after 24 h. It can be concluded that gas-phase CS induces ER stress in A549 alveolar epithelial cells, leading to inadequate protein turnover caused by an accumulation of damaged proteins, reduction in nascent protein synthesis and inhibition of the proteasome. We suggest that prolonged ER stress may lead to excessive cell death with disruption of the epithelial barrier, contributing to development of chronic obstructive pulmonary disease.
authors: Laboratory of Allergology and Pulmonary Diseases, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors: Anita
authors: A
authors: Somborac-Bacura
authors: Marco
authors: M
authors: van der Toorn
authors: Lorenza
authors: L
authors: Franciosi
authors: Dirk-Jan
authors: DJ
authors: Slebos
authors: Tihana
authors: T
authors: Zanic-Grubisic
authors: Rainer
authors: R
authors: Bischoff
authors: Antoon J M
authors: AJ
authors: van Oosterhout
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D012906:Smoke; D014026:Nicotiana; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D012906:Smoke; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex