Oncotarget

Research Papers:

Autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic reticulum stress and oxidative stress

Tao Fan, Lei Chen, Zhixin Huang, Zhangfan Mao, Wei Wang, Boyou Zhang, Yao Xu, Shize Pan, Hao Hu and Qing Geng _

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Oncotarget. 2016; 7:87206-87218. https://doi.org/10.18632/oncotarget.13560

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Abstract

Tao Fan1, Lei Chen1, Zhixin Huang2, Zhangfan Mao1, Wei Wang1, Boyou Zhang1, Yao Xu1, Shize Pan1, Hao Hu1, Qing Geng1

1Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China

2Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China

Correspondence to:

Qing Geng, email: [email protected]

Keywords: apoptosis, autophagy, endoplasmic reticulum stress, hypoxia-reoxygenation, ischaemia-reperfusion

Received: August 02, 2016     Accepted: November 08, 2016     Published: November 24, 2016

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.


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