Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice
| Autor: | Anand Thirupathi, Vitor Hugo Comin, Gustavo de Bem Silveira, Thais F. Luciano, Claudio Teodoro De Souza, Elvis Wisniewski, Schérolin de Oliveira Marques, Paulo Cesar Silveira Lock, Ana Lúcia Bernardo De Carvalho Morsch |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Physiology Blotting Western Clinical Biochemistry Cell Cycle Proteins AMP-Activated Protein Kinases 030204 cardiovascular system & hematology Pharmacology medicine.disease_cause Biochemistry lung Cigarette Smoking ATG12 Mice 03 medical and health sciences 0302 clinical medicine lcsh:Pathology Autophagy medicine Animals lcsh:QH301-705.5 PI3K/AKT/mTOR pathway smoke cigarette chemistry.chemical_classification Reactive oxygen species 030102 biochemistry & molecular biology TOR Serine-Threonine Kinases Biochemistry (medical) AMPK Cell Biology ULK1 Oxidative Stress lcsh:Biology (General) Peroxidases chemistry sestrin Phosphorylation Electrophoresis Polyacrylamide Gel Reactive Oxygen Species Oxidative stress lcsh:RB1-214 Research Article |
| Zdroj: | Redox Report : Communications in Free Radical Research Redox Report, Vol 24, Iss 1, Pp 27-33 (2019) |
| ISSN: | 1743-2928 1351-0002 |
| Popis: | Many pathological conditions linked to cigarette smoking are caused by the production of reactive oxygen species (ROS). The present study was conducted to analyze the effect of ROS on the lungs of Swiss mice exposed to cigarette smoking, focusing on autophagy-mediated mechanisms, and investigate the involvement of SESN2, AMPK, and mTOR signaling. Mice were exposed to cigarette smoke (CS) for 7, 15, 30, 45, and 60 days; the control group was not exposed to CS. Only mice exposed to CS for 45 days were selected for subsequent N-acetylcysteine (NAC) supplementation and smoke cessation analyses. Exposure to CS increased the production of ROS and induced molecular changes in the autophagy pathway, including an increase in phosphorylated AMPK and ULK1, reduction in phosphorylated mTOR, and increases in SESN2, ATG12, and LC3B levels. NAC supplementation reduced ROS levels and reversed all molecular changes observed upon CS treatment, suggesting the involvement of oxidative stress in inducing autophagy upon CS exposure. When exposure to CS was stopped, there were decreases in the levels of oxidative stress, AMPK and ULK1 phosphorylation, and autophagy-initiating molecules and increase in mTOR phosphorylation. In conclusion, these results suggest the involvement of ROS, SESN2, AMPK, and mTOR in the CS-induced autophagic process in the lung. |
| Databáze: | OpenAIRE |
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