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Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial
Citation:
BRUNO, M. E., Y. GE, R. Prasad, AND W. Winnick. Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
To identify oxidative stress-responding toxicity pathways and networks that are associated with exposure to nanomaterials, an integrated redox proteomic study was conducted using human bronchial epithelial cells (BEAS-2B) and titanium dioxide
Description:
Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways and networks that are associated with exposure to nanomaterials, an integrated redox proteomic study was conducted using human bronchial epithelial cells (BEAS-2B) and 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. 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™ (IPA) canonical pathways and IPA tox lists, and these proteins were found to be involved in 20 proteomic pathways/lists. The protein-generated IPA canonical pathways and IPA tox lists 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 oftitanium dioxide. This abstract does not necessarily reflect EPA policy.