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Integrated Proteomic Approaches for Understanding Toxicity of Environmental Chemicals
Citation:
GE, Y. Integrated Proteomic Approaches for Understanding Toxicity of Environmental Chemicals. Presented at EUROTOX 2011, Paris, FRANCE, August 28 - 31, 2011.
Impact/Purpose:
My presentation will focus on the recent application of proteomics technologies and methodologies to identification of modes of action of titanium dioxide.
Description:
To apply quantitative proteomic analysis to the evaluation of toxicity of environmental chemicals, we have developed an integrated proteomic technology platform. This platform has been applied to the analysis of the toxic effects and pathways of many important environmental chemicals including arsenic, bromate, benzo[a]pyrene, nanoparticles, diesel exhaust particles, conazoles and ozone. The endpoints studied include protein expression, protein posttranslational modifications, especially protein oxidation, in mouse and rat liver, lung, thyroid, and kidney tissues as well as human cells. My presentation will focus on the recent application of proteomics technologies and methodologies to identification of modes of action of titanium dioxide. Utilizing two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we identified 46 proteins that were altered at protein expression levels in human bronchial epithelial BEAS-2B cells, exposed to titanium dioxide. 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™ (lPA) canonical pathways and IPA tox lists to create protein interaction networks and proteomic pathways. Twenty protein canonical pathways and tox lists were generated, and these pathways were compared to signaling pathways generated from previous 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. As compared to the control, phosphorylation of the protein kinases such as P38, c-Jun NH(2)-terminal protein kinases (JNK), ERK, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), mitogen-and stress-activated protein kinase (MSK), glycogen synthase kinase (GSK), AMP-activated protein kinase2 (AMPK2), signal transducer and activator of transcription (STATs), and FYN were significantly increased. The present study provides the first protein interaction network maps of the biological responses and potential toxicity and detoxification pathways of titanium dioxide.