Phosphocholine-induced energy source shift alleviates mitochondrial dysfunction in lung cells caused by geospecific PM 2.5 components

Abstract

Fine particulate matter (PM 2.5 ) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM 2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM 2.5 -associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM 2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM 2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM 2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou’s counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM 2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM 2.5 and the critical toxic PM 2.5 components in both regions. Among the PM 2.5 -down-regulated metabolites, phosphocholine emerged as a promising intervention for PM 2.5 cytotoxicities. Its supplementation effectively attenuated PM 2.5 -induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM 2.5 -induced cellular disorder and provided insights into the geo-based variability in toxic PM 2.5 components.