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

Area of Science:

• Molecular Biology
• Cellular Biology
• Toxicology

Background:

• Cigarette smoking is linked to numerous pathologies, often driven by reactive oxygen species (ROS) production.
• Autophagy, a cellular degradation process, is implicated in lung injury but its specific mechanisms in smoking-induced damage require further elucidation.

Purpose of the Study:

• To investigate the impact of cigarette smoke (CS) exposure on ROS production and autophagy in mouse lungs.
• To explore the roles of SESN2, AMPK, and mTOR signaling pathways in CS-induced autophagy.
• To assess the effects of N-acetylcysteine (NAC) supplementation and smoke cessation on these molecular changes.

Main Methods:

• Swiss mice were exposed to CS for varying durations (7-60 days).
• Specific groups received N-acetylcysteine (NAC) or underwent smoke cessation after 45 days of CS exposure.
• Molecular analysis focused on ROS levels, autophagy markers (ATG12, LC3B), and signaling proteins (SESN2, p-AMPK, p-ULK1, p-mTOR).

Main Results:

• CS exposure elevated ROS levels and modulated autophagy, increasing p-AMPK, p-ULK1, SESN2, ATG12, and LC3B, while decreasing p-mTOR.
• NAC treatment reduced ROS and reversed CS-induced molecular alterations, indicating oxidative stress's role in autophagy.
• Smoke cessation decreased oxidative stress, AMPK/ULK1 phosphorylation, and autophagy markers, alongside increased mTOR phosphorylation.

Conclusions:

• Reactive oxygen species (ROS) play a critical role in mediating cigarette smoke-induced autophagy in the lungs.
• The SESN2, AMPK, and mTOR signaling pathways are significantly involved in the autophagic response to CS exposure.
• Interventions targeting oxidative stress and promoting smoke cessation can modulate these pathways, offering potential therapeutic avenues.