Acetaldehyde Induced Cell Damage and Genotoxic Effects by Modulating PI3K/AKT and MAPK/ERK Pathways in Human Lung Epithelial Cells

Long-term acetaldehyde exposure is associated with cell death, oxidative stress, and DNA damage in lung injury such as chronic obstructive pulmonary disease and respiratory distress syndrome, but the signal transduction mechanism linking key processes remains largely unknown. This study aims to reveal molecular mechanisms of cytotoxicity and genotoxicity induced by acetaldehyde based on human bronchial epithelial cells. Firstly, RNA-seq analysis indicated that differentially expressed genes are most enriched in MAPK/ERK and PI3K/AKT pathways. Secondly, significant up-regulation of four key signaling proteins was confirmed. Subsequently, we found that inhibitors of these pathways could significantly reduce cytotoxicity, oxidative stress, and genotoxicity induced by acetaldehyde. Finally, gene silencing was employed to further validate the importance of these pathways, and toxic effects were more effectively alleviated. Our research suggests that acetaldehyde-induced cell damage and genotoxic effects through PI3K/AKT and MAPK/ERK pathways, provide new insights into toxic mechanisms of acetaldehyde-induced lung injury. Overall design: RNA-seq profiling of wild-type BEAS-2B cells exposed to acetaldehyde (0, 10, and 16 mM) for 24 hours.