Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats

Raja Sekhar Nirujogi, James D. Wright, Srikanth S. Manda, Jun Zhong, Chan Hyun Na, James Meyerhoff, Bernard Benton, Rabih Jabbour, Kristen Willis, Min Sik Kim, Akhilesh Pandey, Jennifer W. Sekowski

Research output: Contribution to journalArticle

Abstract

To gain insights into the toxicity induced by the nerve agent VX, an MS-based phosphoproteomic analysis was carried out on the piriform cortex region of brains from VX-treated rats. Using isobaric tag based TMT labeling followed by titanium dioxide enrichment strategy, we identified 9975 unique phosphosites derived from 3287 phosphoproteins. Temporal changes in the phosphorylation status of peptides were observed over a time period of 24 h in rats exposed to a 1× LD50, intravenous (i.v.) dose with the most notable changes occurring at the 1 h postexposure time point. Five major functional classes of proteins exhibited changes in their phosphorylation status: (i) ion channels/transporters, including ATPases, (ii) kinases/phosphatases, (iii) GTPases, (iv) structural proteins, and (v) transcriptional regulatory proteins. This study is the first quantitative phosphoproteomic analysis of VX toxicity in the brain. Understanding the toxicity and compensatory signaling mechanisms will improve the understanding of the complex toxicity of VX in the brain and aid in the elucidation of novel molecular targets that would be important for development of improved countermeasures. All MS data have been deposited in the ProteomeXchange with identifier PXD001184 (http://proteomecentral.proteomexchange.org/dataset/PXD001184).

Original languageEnglish (US)
Pages (from-to)487-499
Number of pages13
JournalProteomics
Volume15
Issue number2-3
DOIs
StatePublished - Jan 1 2015

Keywords

  • Animal proteomics
  • Phosphoproteomics
  • Piriform cortex
  • Signal transduction
  • VX

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Nirujogi, R. S., Wright, J. D., Manda, S. S., Zhong, J., Na, C. H., Meyerhoff, J., Benton, B., Jabbour, R., Willis, K., Kim, M. S., Pandey, A., & Sekowski, J. W. (2015). Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats. Proteomics, 15(2-3), 487-499. https://doi.org/10.1002/pmic.201400371