title: Endoplasmic reticulum stress and apoptosis via PERK-eIF2α-CHOP signaling in the methamphetamine-induced chronic pulmonary injury.
abstract: Methamphetamine (MA) leads to multiple organs lesions and apoptosis. The aim of this study is to investigate if endoplasmic reticulum stress (ERS) - initiated apoptosis is involved in the chronic pulmonary injury induced by MA. In this study, rats were divided into a control group, methamphetamine 5mg/kg group and methamphetamine 10mg/kg group. This study found that the protein level of GRP78 is higher in M10 group than in control group. PERK signaling and the relevant apoptosis factors were also activated. Morphological measurements showed that protein BAX and CHOP accumulated in the alveolar epithelium and the alveolar walls with epithelium were damaged and that the number of pulmonary alveoli decreased. The findings showed that ERS and PERK pathway are activated and eventually lead to apoptosis. Severe ERS mediated the apoptosis of alveolar epithelium cells as well as decreasing numbers of pulmonary alveoli.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, China.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Gu
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, China. Electronic address: ywang28@cmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Drug Control, China Criminal Police University, Shenyang 110035, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, China; National Key Subject, Institute of Respiratory Diseases, China Medical University, Shenyang, China.
authors.forename: Huai-Liang
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017208:Rats, Wistar; D051742:Transcription Factor CHOP / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D008694:Methamphetamine; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C497251:Ddit3 protein, rat
keywords: Apoptosis; CHOP; Chronic pulmonary injury; Endoplasmic reticulum stress; Methamphetamine; PERK/eIF2α