Proteomics Analysis Revealed the Damage Mechanism of Hexavalent Uranium on BEAS-2B Cells through Oxidative Stress

Hexavalent uranium (U(VI)) is widely found in nature and has an impact on human lung health. In this study, the proteomic changes in lung epithelial BEAS-2B cells exposed to U(VI) were evaluated using DIA (Data-Independent Acquisition) proteomics. BEAS-2B cells cultured in vitro were exposed to 0, 200, 400, and 700 mg/L U(VI) for 24 h, and differential proteins were identified by classification, KEGG pathway enrichment, and GO enrichment analysis. Furthermore, oxidative stress levels were measured, and five proteins were screened for validation. The results indicated that the number of differential proteins increased with the increase of the U(VI) dose. The differentially expressed proteins (DEPs) identified in the GJL vs Control comparison were significantly enriched in several KEGG pathways, including the PI3K-Akt signaling pathway, pathways in cancer, cell cycle, lysosome, and JAK-STAT signaling pathway. The DEPs related to the nucleoplasm, nucleus, and cytoskeleton were found to be enriched in several biological processes, including the cell cycle, positive regulation of transcription by RNA polymerase II, cell division, and cell migration. Differential proteins involve multiple organelles, and their functions are mostly related to protein binding. Furthermore, the ROS level increased, and the GSH was reduced. The expressions of STAT3, N-cadherin, and CDK2 proteins were down-regulated, and the expressions of GPX3 and TNFSF10B were up-regulated. This study provides a comprehensive understanding of the molecular mechanisms underlying U(VI)-induced pulmonary epithelial cytotoxicity.