title: Autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress.
abstract: To study the impact of autophagy on alveolar macrophage apoptosis and its mechanism in the early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar macrophages stably expressing RFP-LC3 were treated with autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment 2 h, 4 h or 6 h later. Twenty Sprague-Dawley male rats were randomly divided into four different groups: no blocking of left lung hilum (model group), left lung hilum blocked for 1h with DMSO lavage (control group), left lung hilum blocked for 1 h with 100 ml/kg 3-MA (5 μmol/L) lavage (3-MA group), and left lung hilum blocked for 1 h with 100 ml/kg rapamycin (250 nmol/L) lavage (rapamycin group). Rapamycin decreased the unfolded protein response, which reduced endoplasmic reticulum stress-mediated apoptosis in the presence of oxygen deficiency. Rapamycin increased superoxide dismutase activities and decreased malondialdehyde levels, whereas 3-MA decreased superoxide dismutase activities and increased malondialdehyde levels. Thus, autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress in the early stage of hypoxia in vitro and in vivo. This could represent a new approach to protecting against lung ischemia-reperfusion injury.
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Fan
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Zhangfan
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Boyou
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Shize
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Geng
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C025946:3-methyladenine; D013482:Superoxide Dismutase; D053148:Caspase 3; D000225:Adenine; D020123:Sirolimus
keywords: apoptosis; autophagy; endoplasmic reticulum stress; hypoxia-reoxygenation; ischaemia-reperfusion