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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)

2011-10-29 | GSE33325 | GEO

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.

2011-10-28 | E-GEOD-33325 | biostudies-arrayexpress

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

2011-10-21 | GSE33109 | GEO

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.

2011-10-20 | E-GEOD-33109 | biostudies-arrayexpress

Drug-induced hepatotoxicity screening in primary mouse hepatocytes, an Omics approach.

Project description:Drug-induced hepatotoxicity is a leading cause of attrition of candidate drugs in drug development. Therefore new screening methods are necessary which predict these hazards more accurate and earlier in the drug development process. Of all in vitro hepatotoxicity models, primary human hepatocytes are considered as 'the gold standard'. However, the use of these hepatocytes is hindered by their scarcity and major inter-individual variation. These limitations may be overcome with use of primary mouse hepatocytes. Within this context changes in protein expressions in primary mouse hepatocytes, after exposure to cyclosporin A were studied using differential gel electrophoresis. Thereafter, the mRNA expression levels of these deregulated proteins from cyclosporin A-treated cells were analyzed. Cyclosporin A induced ER stress and altered the ER-Golgi transport, which may alter vesicle mediated transport and protein secretion. Moreover are the differentially expressed proteins observed upon challenge by cyclosporin A, associated with cholestatic mechanisms. For each biological experiment, one hybridization was conducted and one sample per array. In total, 6 arrays were used for 2 different conditions (Csa or control at 48 hours).

2013-04-01 | E-GEOD-33742 | biostudies-arrayexpress

Drug-induced hepatotoxicity screening in primary mouse hepatocytes, an Omics approach.

2013-04-01 | GSE33742 | GEO

Genome-wide analysis of gene expression in influenza A infected human macrophages treated with VX-787

2016-04-03 | GSE79854 | GEO

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.

2015-01-07 | PXD001184 | Pride

Genome-wide analysis of gene expression in influenza A infected human macrophages treated with VX-787

Project description:Analysis of gene expression in macrophages infected with influenza A virus or Mock and treated with the VX-787 to investigate the effects VX-787 have on transcriptional response in human macrophages. Human macrophages were infected with influenza A/WSN/1933(H1N1) or A/Udorn/307/72(H3N2) viruses, or non-infected (Mock). 10nM VX-787 was treated to WSN, Udorn or Mock infected cells, repectively.

2016-04-03 | E-GEOD-79854 | biostudies-arrayexpress

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