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Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles
Citation:
ORTIZ, P. A., M. E. BRUNO, T. MOORE, S. NESNOW, W. M. WINNIK, AND Y. Ge. Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles. Journal of Proteome Research . American Chemical Society, Washington, DC, 9(3):1268-1278, (2010).
Impact/Purpose:
A large number of differential studies have been undertaken to describe changes of protein expression in hepatic cells or liver tissues treated with various environmental toxicants including carcinogens. Utilizing 2-DE, immunoblotting, and MS, we have previously identified 17 carbonylated proteins that were altered with varying intensities in the livers of mice treated with propiconazole. We have recently completed a comparative transcriptomic evaluation of several mouse liver tumorigenic conazoles including propiconazole. To expand our previous studies on identification propiconazole toxicity pathways, we performed this study on identification of protein expression profiles in mice treated with propiconazole.
Description:
We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this fungicide. Utilizing twodimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we identified 62 proteins that were altered. Several of these protein changes detected by 2-DE/MS were verified by Westemblot analyses. These differentially expressed proteins were mapped using Ingenuity Pathway Analyses" (IPA) canonical pathways and IPA tox lists. Forty-four pathways/lists were identified. IPA was also used to create networks of interacting protein clusters. The proteingenerated IPA canonical pathways and IPA tox lists were compared to those pathways and lists previously generated from genomic analyses from livers of mice treated with propiconazole under the same experimental conditions. There was a significant overlap in the specific pathways and lists generated from the proteomic and the genomic data with 27 pathways common to both proteomic and genomic analyses. However, there were also 17 pathways/lists identified only by proteomics analysis and 21 pathways/lists only identified by genomic analysis. The protein network analysis produced interacting sub-networks centered around hepatocyte nuclear factor 4a (HNF4a), MYC, proteasome subunit type 4a, and glutathione S-transferase (GST). The HNF4a network hub was also identified by genomic analysis. Five GST isoforms were identified by proteomic analysis and GSTs were present in 10 of the 44 protein-based pathways/lists. Hepatic GST activities were compared between mice treated with propiconazole and 2 additional conazoles and higher GST activities were found to be associated with the tumorigenic conazoles.
