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Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide
Citation:
GE, Y., M. E. BRUNO, K. WALLACE, W. M. WINNIK, AND R. Y. Prasad. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide. Presented at Society of Environmental Toxicology and Chemistry (SETAC) Annual Meeting, Milan, ITALY, May 15 - 19, 2011.
Impact/Purpose:
To identify 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.
Description:
Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify 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 two-dimensional gel electrophoresis (2-DE) and mass spectrometry (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. The identified proteins include some key proteins involved in cellular stress response, metabolism, adhesion, cytoske1etal dynamics, cell growth, cell death, and cell signaling. These differentially expressed proteins were also mapped to identify potential toxicity pathways of titanium dioxide using Ingenuity Pathways Analysis?' (IPA). Twenty protein canonical pathways and tox lists were generated from the analysis, 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 dioxidetreated 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. This abstract does not necessarily reflect EPA policy.