Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice

Abstract

2019) Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice, ABSTRACT 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.

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

“…After exposure to cellular stress, increased levels of SESN2 can activate AMPK, resulting in the negative regulation of mTOR [ 132 ]. Morsch and colleagues [ 133 ] observed reduced SESN2 protein levels and AMPK phosphorylation, and increased mTOR phosphorylation in mice exposed to cigarette smoking for 45 days. Furthermore, mTORC2 activity is also sensitive to the redox state [ 134 ].…”

Autophagy-related gene P4HB: a novel diagnosis and prognosis marker for kidney renal clear cell carcinoma

“…When stimulated by starvation and hypoxia, defective organelles are separated from cytoplasm and encircled by autophagosome (a doublemembrane vesicle) [7]. Autophagosomes could mature by fusing with lysosomes to become autolysosomes which contain hydrolases to degrade the components encircled [8][9][10]. Depending on the conditions, autophagy has both protective and harmful effects including pro-or anti-tumor effects.…”

Emerging Clues of Regulatory Roles of Circular RNAs through Modulating Oxidative Stress: Focus on Neurological and Vascular Diseases

“…ROS produced during oxidative stress causes oxidative damage to cells. ROS is increased in and associated with various risk factors of neurovascular diseases [13][14][15][16]. The roles of cir-cRNAs in modulating oxidative stress have been discovered in both the basic and clinical studies (Table 1), and circRNAs are widely involved in different molecular mechanisms contributing to the pathophysiological processes of neurovascular disease [12,68].…”

“…This pathological process is closely related to neurovascular diseases. Various risk factors of neurovascular diseases, such as smoking [ 13 ], fluctuation of blood glucose levels [ 14 ], hypertension [ 15 ], and hyperhomocysteinemia [ 16 ], can all increase ROS production. Accumulating evidence indicates that circRNAs are involved in the process of oxidative stress [ 17 ] and may be an important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions of neurological diseases.…”