Dataset Information

Phosphoproteomic Analysis Suggests Compensatory Effects in the Piriform Cortex Region of the VX-Exposed Rat

ABSTRACT: To gain insight into the toxicity induced by VX, a mass spectrometry based phosphoproteomics approach was employed to understand the signaling modulated by VX toxicity in piriform cortex region of the rat brain. We have employed isobaric-based TMT labeling and titanium dioxide- based enrichment strategy to identify and quantify the changes that are modulated by VX. We observed a temporal association of changes in the phosphorylation status of proteins over a 24 hour time course in rats exposed to 1x LD50 VX, with the most notable changes by the first measured time point, 1 hour post exposure. These data fell into five main functional classes of proteins directly or indirectly influenced by changes in phosphorylation: 1) Ion channels/transporters, including ATPases, 2) Kinases/Phosphatases, 3) GTPases, 4) Structural related proteins, and 5) Transcriptional regulatory proteins. This study is the first quantitative phosphoproteomics 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 allowing for improved countermeasure development.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Piriform Area

SUBMITTER: Jennifer Sekowski

LAB HEAD: Jennifer W. Sekowski

PROVIDER: PXD001184 | Pride | 2015-01-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	ECBC_PC_RatVX_8TMT_TiO2_bRPLC_All_SequestHT_Mascot_052314.pep.xml	Pepxml
	ECBC_PC_RatVX_8TMT_TiO2_bRPLC_All_SequestHT_Mascot_052314.prot.xml	Xml
	ECBC_PC_RatVX_8TMT_TiO2_bRP_1.raw	Raw
	ECBC_PC_RatVX_8TMT_TiO2_bRP_10.raw	Raw
	ECBC_PC_RatVX_8TMT_TiO2_bRP_11.raw	Raw

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Publications

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

Nirujogi Raja Sekhar RS Wright James D JD Manda Srikanth S SS Zhong Jun J Na Chan Hyun CH Meyerhoff James J Benton Bernard B Jabbour Rabih R Willis Kristen K Kim Min-Sik MS Pandey Akhilesh A Sekowski Jennifer W JW

Proteomics 20150101 2-3

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 wi ...[more]

PMID: 25403869

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