Analysis of Nicotine Toxicity and Mechanisms of Senescence in Nucleus Pulposus Cells Using Network Toxicology and Molecular Docking Technique

Abstract

Aim

Through the use of network toxicology, the research sought to determine whether cellular senescence and associated molecular mechanisms in nicotine-induced intervertebral disc degeneration (IVDD) were potentially harmful.

Methods

The primary chemical structure and 105 targets of action of nicotine were determined by using the Swiss Target Prediction, Cell Age, and PubChem databases. 855 IVDD senescence genes were found using the GEO and Cell Age datasets.

Results

After additional screening and Cytoscape development, 9 key targets were identified. Additionally, these targets' co-expression pattern analysis and protein interactions were confirmed to be identical. The core targets of nicotine-induced IVDD cellular senescence were found to be primarily enriched in the positive regulation of cell proliferation, telomere shortening, histone acetylation, and cellular senescence-related processes, according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The KEGG signaling pathway also made it clear that the Apelin signaling route, nicotinate and nicotinamide metabolism, cell cycle, and apoptosis are all strongly linked to nicotine-induced IVDD cellular senescence. We chose four genes associated with the cellular senescence pathway—HDAC1, HDAC4, and NAMPT, MYLK—for molecular docking with the toxic substance nicotine. The findings validated nicotine's strong affinity for the primary targets.

Conclusion

All things considered, the current research indicates that nicotine may contribute to cellular senescence in IVDD via controlling the histone deacetylation process, telomere shortening, the Apelin signaling pathway, and pathways linked to the metabolism of nicotinate and nicotinamide. The theoretical foundation for investigating the molecular mechanisms of nicotine-induced senescence in IVDD is established.