14,15-Epoxyeicosatrienoic Acid Suppresses Cigarette Smoke Extract-Induced Apoptosis in Lung Epithelial Cells by Inhibiting Endoplasmic Reticulum Stress

• Published in: Cellular physiology and biochemistry Vol. 36; no. 2; pp. 474 - 486
• Main Authors: Yu, Ganggang, Zeng, Xiangjun, Wang, Hongxia, Hou, Qi, Tan, Chunting, Xu, Qiufen, Wang, Haoyan
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01-05-2015
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - pharmacology; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line; Cigarette smoke; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450 2J2; Endoplasmic Reticulum Chaperone BiP; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epoxyeicosatrienoic acids; Humans; Lung - cytology; Lung - drug effects; Nicotiana - chemistry; Original Paper; Reactive Oxygen Species - metabolism; Smoke - adverse effects; Smoking - adverse effects; Smoking - metabolism; Epoxyeicosatrienoic acids; Cytochrome P450 2J2; Cigarette smoke; Apoptosis; Endoplasmic reticulum stress
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000430113

Background/Aims: Epoxyeicosatrienoic acids (EETs), a type of lipid mediators produced by cytochrome P450 epoxygenases, exert anti-inflammatory, angiogenic, anti-oxidative and anti-apoptotic effects. However, the role of EETs in cigarette smoke-induced lung injury and the underlying mechanisms are not fully known. The aim of this study was to explore the effects of CYP2J2-EETs on cigarette smoke extracts (CSE)-induced apoptosis in human bronchial epithelial cell line (Beas-2B) and the possible mechanisms involved. Methods: Cytochrome P450 epoxygenase 2J2 (CYP2J2) and its metabolites EETs were assessed by western blotting or LC-MS-MS. Cell viability and apoptosis were determined by MTT assay and AnnexinV-PI staining. Reactive oxygen species (ROS) were assessed by measuring H2DCFDA. Caspase-3, HO-1, MAPK and endoplasmic reticulum (ER) stress-related markers GRP78, p-elF2a, and CHOP were evaluated by western blotting. Results: CSE suppressed expression of both CYP2J2 and EET by Beas-2B cells. CSE also induced apoptosis, the generation of ROS and the ER stress in Beas-2B cells. These changes were abolished by pretreatment with exogenous 14,15-EET while pretreatment with 14,15-EEZE, a selective EET antagonist, abolished the protective effects of 14,15-EET. In addition, EETs increased the expression of antioxidant enzyme HO-1. Furthermore, 14,15-EET reduced CSE-induced activation of p38 and JNK. Conclusion: The data suggest that CYP2J2-derived EETs protect against CSE-induced lung injury possibly through attenuating ER stress.