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Broad spectrum proteomics analysis of the inferior Colliculus following acute hydrogen sulfide exposure

Dong-Suk Kim, Poojya Anantharam, Andrea Hoffman, Mitchell L Meade, Nadja Grobe, Jeffery M Gearhart, Elizabeth M Whitley, Belinda Mahama, Wilson K Rumbeiha
doi: https://doi.org/10.1101/237370
Dong-Suk Kim
Veterinary Diagnostic & Production Animal Medicine, Iowa State University;
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Poojya Anantharam
Veterinary Diagnostic & Production Animal Medicine, Iowa State University;
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Andrea Hoffman
Henry M Jackson Foundation; 711HPW/USAFSAM/FHOF, Wright Patterson AFB;
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Mitchell L Meade
711HPW/RHDJ, Wright Patterson Air Force Base, Dayton, OH, US;
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Nadja Grobe
711HPW/RHDJ, Wright Patterson Air Force Base, Dayton, OH, US;
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Jeffery M Gearhart
711HPW/RHDJ, Wright Patterson Air Force Base, Dayton, OH, US;
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Elizabeth M Whitley
Pathogenesis, LLC, Gainesville, FL, US
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Belinda Mahama
Veterinary Diagnostic & Production Animal Medicine, Iowa State University;
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Wilson K Rumbeiha
Veterinary Diagnostic & Production Animal Medicine, Iowa State University;
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  • For correspondence: rumbeiha@iastate.edu
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Abstract

Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders. The mechanisms of H2S-induced neurodegeneration are not known. To better understand the cellular and molecular mechanisms of H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to search for key molecules in H2S-induced neurotoxicity. Mice were subjected to acute whole body exposure of up to 750 ppm of H2S. The H2S-treated group showed behavioral motor deficits and developed severe lesions in the inferior colliculus (IC), part of the brainstem. The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS was able to identify 598, 562, and 546 altered proteomic changes for day 1 (2 h post H2S exposure), day 2, and day 4 of H2S exposure, respectively. Mass spectrometry data were analyzed by Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Quantitative real-time PCR was used to confirm some of the H2S-dependent proteomics changes. Taken together, acute exposure to H2S induced behavioral motor deficits along with progressive neurodegeneration including disruption of several biological processes in the IC such as cellular morphology, energy metabolism, and calcium signaling. The obtained broad-spectrum proteomics data may provide important clues to elucidate mechanisms of H2S-induced neurotoxicity.

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The copyright holder for this preprint is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
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  • Posted December 28, 2017.

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Broad spectrum proteomics analysis of the inferior Colliculus following acute hydrogen sulfide exposure
Dong-Suk Kim, Poojya Anantharam, Andrea Hoffman, Mitchell L Meade, Nadja Grobe, Jeffery M Gearhart, Elizabeth M Whitley, Belinda Mahama, Wilson K Rumbeiha
bioRxiv 237370; doi: https://doi.org/10.1101/237370
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Broad spectrum proteomics analysis of the inferior Colliculus following acute hydrogen sulfide exposure
Dong-Suk Kim, Poojya Anantharam, Andrea Hoffman, Mitchell L Meade, Nadja Grobe, Jeffery M Gearhart, Elizabeth M Whitley, Belinda Mahama, Wilson K Rumbeiha
bioRxiv 237370; doi: https://doi.org/10.1101/237370

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