TY - JOUR
T1 - Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure
AU - Kim, Dong Suk
AU - Anantharam, Poojya
AU - Hoffmann, Andrea
AU - Meade, Mitchell L.
AU - Grobe, Nadja
AU - Gearhart, Jeffery M.
AU - Whitley, Elizabeth M.
AU - Mahama, Belinda
AU - Rumbeiha, Wilson K.
N1 - Funding Information:
This work was partially supported by the Iowa State University College of Veterinary Medicine Seed grant, Startup funds and incentive account funds for Rumbeiha.
Publisher Copyright:
© 2018 The Authors
PY - 2018/9/15
Y1 - 2018/9/15
N2 - Acute exposure to high concentrations of H 2 S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H 2 S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H 2 S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H 2 S. H 2 S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). 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 identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H 2 S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H 2 S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H 2 S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H 2 S-induced neurotoxicity.
AB - Acute exposure to high concentrations of H 2 S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H 2 S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H 2 S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H 2 S. H 2 S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). 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 identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H 2 S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H 2 S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H 2 S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H 2 S-induced neurotoxicity.
KW - Hydrogen sulfide
KW - Neurodegeneration
KW - Neurotoxicity
KW - Proteomic analysis
KW - Proteomic profiling
KW - TMT labeled LC-MS/MS
UR - http://www.scopus.com/inward/record.url?scp=85049008438&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049008438&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2018.06.001
DO - 10.1016/j.taap.2018.06.001
M3 - Article
C2 - 29932956
AN - SCOPUS:85049008438
SN - 0041-008X
VL - 355
SP - 28
EP - 42
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
ER -