Open AccessmTOR‐autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine
Author(s) -
Zhu MeiJia,
Liu BingYang,
Shi Lin,
Wang Xin,
Wang Yun
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15841
Subject(s) - autophagy , pi3k/akt/mtor pathway , senescence , microbiology and biotechnology , western blot , chemistry , biology , cancer research , signal transduction , apoptosis , biochemistry , gene
It is growingly concerned about methamphetamine (MA)‐induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA‐induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR‐autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß‐galactosidase staining, cell cycle detection, transfection and co ‐ immunoprecipitation. Long‐term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3‐I to LC3‐II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co ‐ immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up‐regulating p21 and p53, arresting cell cycle and increasing SA‐β‐gal. Overexpression of IMP1 reduced p21 and SA‐β‐gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR‐autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.