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内质网应激与甲基苯丙胺诱导的慢性肺损伤中通过PERK-eIF2α-CHOP信号通路介导的细胞凋亡

Endoplasmic reticulum stress and apoptosis via PERK-eIF2α-CHOP signaling in the methamphetamine-induced chronic pulmonary injury.

作者信息

Gu Yu-Han, Wang Yun, Bai Yang, Liu Ming, Wang Huai-Liang

机构信息

Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, China.

Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning Province, China.

出版信息

Environ Toxicol Pharmacol. 2017 Jan;49:194-201. doi: 10.1016/j.etap.2017.01.003. Epub 2017 Jan 3.

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.

摘要

甲基苯丙胺(MA)会导致多器官损伤和细胞凋亡。本研究的目的是探究内质网应激(ERS)引发的细胞凋亡是否参与MA诱导的慢性肺损伤。在本研究中,大鼠被分为对照组、5mg/kg甲基苯丙胺组和10mg/kg甲基苯丙胺组。本研究发现,M10组中GRP78的蛋白水平高于对照组。PERK信号通路及相关凋亡因子也被激活。形态学测量显示,蛋白BAX和CHOP在肺泡上皮细胞中积累,上皮细胞所在的肺泡壁受损,肺泡数量减少。研究结果表明,ERS和PERK通路被激活并最终导致细胞凋亡。严重的ERS介导了肺泡上皮细胞的凋亡以及肺泡数量的减少。

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