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Gene expression changes in human hepatocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

ABSTRACT: Organophosphorus compounds induce hepatotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human hepatocytes after exposure to VX, and identified pathways underlying these changes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33606 | GEO | 2011/11/11

SECONDARY ACCESSION(S): PRJNA148529

REPOSITORIES: GEO

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Gene expression changes in human hepatocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

Project description:Organophosphorus compounds induce hepatotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human hepatocytes after exposure to VX, and identified pathways underlying these changes. Human hepatocytes were exposed to sublethal concentrations (0, 0.1, 10 μM) of VX. RNA were extracted at different timepoints (0, 6 h) after VX exposure and hybridized to Affymetrix microarrays. Four biological repeats were used for each condition.

2011-11-11 | E-GEOD-33606 | biostudies-arrayexpress

Gene expression changes in human cardiomyocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

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Gene expression changes in human cardiomyocytes exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

Project description:Organophosphorus compounds induce cardiotoxicity through currently unknown mechanisms, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human cardiomyocytes after exposure to VX, and identified pathways underlying these changes. Human cardiomyocytes were exposed to sublethal concentrations (0, 0.1, 10 μM) of VX. RNA were extracted at different timepoints (0, 6, 24, 72 h) after VX exposure and hybridized to Affymetrix microarrays. Four biological repeats were used for each condition.

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Gene expression changes in human neural cells exposed to VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate)

Project description:Organophosphorus compounds may induce neurotoxicity through mechanisms other than the cholinergic pathway, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human neural cells after exposure to VX, and identified pathways underlying these changes. Human neural cells were exposed to sublethal concentrations (0, 0.1, 10 μM) of VX. RNA were extracted at different timepoints (0, 6, 24, 72 h) after VX exposure and hybridized to Affymetrix microarrays. Four biological repeats were used for each condition.

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

Project description: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.

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microRNA (miRNA) expression data from induced pluripotent stem cell (iPSC)-derived neurons exposed to VX

Project description:Chemical warfare nerve agents (CWNA) are potent cholinesterase inhibitors that may also have non-cholinesterase effects. Several in vivo studies have shown that exposure to CWNA compounds induces damage in the brain and heart. Underlying mechanisms of this damage are a critical area of research for the development of medical countermeasures. This study utilized microRNA (miRNA) analysis to evaluate potential direct cellular effects of the nerve agent VX (o-ethyl-s-[2 (diisopropylamino) ethyl] methylphosphonothiolate) on human-induced pluripotent stem cell (iPSC)-derived neurons iPSC-derived neurons were treated with VX at concentrations of 0µM (saline control), 0.1µM or 100µM for either 1 hour or 6 hours. Total RNA was then isolated and processed for miRNA microarray analysis using Affymetrix miRNA 2.0 GeneChips

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