Abstract
Oxidative stress is known to play important roles in engineered nanomaterial-induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify these toxicity pathways and networks that are associated with exposure to engineered nanomaterials, an integrated proteomic study was conducted using human bronchial epithelial cells, BEAS-2B and nanoscale titanium dioxide. Utilizing 2-DE and MS, we identified 46 proteins that were altered at protein expression levels. The protein changes detected by 2-DE/MS were verified by functional protein assays. These identified proteins include some key proteins involved in cellular stress response, metabolism, adhesion, cytoskeletal dynamics, cell growth, cell death, and cell signaling. The differentially expressed proteins were mapped using Ingenuity Pathway Analyses™ canonical pathways and Ingenuity Pathway Analyses tox lists to create protein-interacting networks and proteomic pathways. Twenty protein canonical pathways and tox lists were generated, and these pathways were compared to signaling pathways generated from genomic analyses of BEAS-2B cells treated with titanium dioxide. There was a significant overlap in the specific pathways and lists generated from the proteomic and the genomic data. In addition, we also analyzed the phosphorylation profiles of protein kinases in titanium dioxide-treated BEAS-2B cells for a better understanding of upstream signaling pathways in response to the titanium dioxide treatment and the induced oxidative stress. In summary, the present study provides the first protein-interacting network maps and novel insights into the biological responses and potential toxicity and detoxification pathways of titanium dioxide.