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

Autor: Belinda Mahama, Dong Suk Kim, Elizabeth M. Whitley, Nadja Grobe, Mitchell L Meade, Wilson K. Rumbeiha, Andrea Hoffmann, Jeffery M. Gearhart, Poojya Anantharam
Rok vydání: 2018
Předmět:
Inferior colliculus
0301 basic medicine
Proteomics
Male
Gene Expression
Tandem mass tag
Inbred C57BL
Toxicology
Mice
Liquid chromatography–mass spectrometry
2.1 Biological and endogenous factors
Hydrogen Sulfide
Aetiology
Inhalation Exposure
Hydrogen sulfide
Behavior
Animal
Chemistry
Neurodegeneration
Pharmacology and Pharmaceutical Sciences
Cell biology
Neurological
Neurotoxicity Syndromes
Brainstem
Signal transduction
Proteomic profiling
Intracranial Hemorrhages
Signal Transduction
Biotechnology
Neurotoxicity Syndrome
Quantitative proteomics
Proteomic analysis
Article
03 medical and health sciences
Seizures
medicine
Neurotoxicity
Animals
TMT labeled LC-MS/MS
Pharmacology
Behavior
Proteomic Profiling
Animal
Neurosciences
medicine.disease
equipment and supplies
Inferior Colliculi
Mice
Inbred C57BL
Oxidative Stress
030104 developmental biology
Zdroj: Toxicology and applied pharmacology
Popis: 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 to750 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.HighlightsMice exposed to H2S recapitulated H2S-induced neurotoxicity manifested in humans.The IC in the mouse brain is the most sensitive to H2S-induced neurodegeneration.Proteomic expressions of key proteins were validated at transcription level.Several biological pathways were dysregulated by H2S exposure.
Databáze: OpenAIRE
Externí odkaz: