title: Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.
abstract: Organophosphorus (OP) compounds represent an important group of chemical warfare nerve agents that remains a significant and constant military and civilian threat. OP compounds are considered acting primarily via cholinergic pathways by binding irreversibly to acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Many studies over the past years have suggested that other mechanisms of OP toxicity exist, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. Here we performed a microarray study in which cultured human neural cells were exposed to 0.1 or 10 μM of VX for 1 h. Global gene expression changes were analyzed 6, 24, and 72 h post exposure. Functional annotation and pathway analysis of the differentially expressed genes has revealed many genes, networks and canonical pathways that are related to nervous system development and function, or to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In particular, the neuregulin pathway impacted by VX exposure has important implications in many nervous system diseases including schizophrenia. These results provide useful information valuable in developing suitable antidotes for more effective prevention and treatment of, as well as in developing biomarkers for, VX-induced chronic neurotoxicity.
authors: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. xiugong.gao@amedd.army.mil
authors: Xiugong
authors: X
authors: Gao
authors: Hsiuling
authors: H
authors: Lin
authors: Radharaman
authors: R
authors: Ray
authors: Prabhati
authors: P
authors: Ray
mesh_terms: D002478:Cells, Cultured; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*
chemical_list: D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; C009680:VX-agent