E-cigarette aerosols induce the hydrolysis of lysosomal glycerophospholipids through PLA2G4A activation initiated by nicotine binding to CHRNA3/α3 nAchr in airway epithelial cells - PubMed
2 hours ago
- #lysosomal dysfunction
- #nicotine toxicity
- #e-cigarette aerosols
- Nicotine in e-cigarette aerosols is the key component causing apoptosis, oxidative stress, and mucus overproduction in airway epithelial cells.
- Nicotine induces autophagosome formation via MTOR inhibition but suppresses autolysosomal degradation through lysosomal membrane permeabilization (LMP).
- LMP is caused by nicotine binding to CHRNA3/α3 nAChR, leading to calcium-dependent activation of PLA2G4A, which hydrolyzes lysosomal glycerophospholipids.
- Restoring lysosomal integrity reverses LMP, alleviates autophagy inhibition, and reduces airway epithelial damage.
- Inhibition of CHRNA3 reduces intracellular Ca2+, prevents PLA2G4A activation, and attenuates LMP and cytotoxicity.
- CHRNA3-mediated PLA2G4A activation and autophagy-lysosome dysfunction are validated in human lung organoids.
- CHRNA3 activation is a molecular initiating event, and its inhibition could be a potential therapy for e-cigarette-induced airway disorders.