title: Transcriptional induction of cholinesterase expression and protection against chemical warfare nerve agents.
abstract: We investigated whether transcriptional inducers could enhance the expression of acetylcholinesterase (AChE) in cell lines to achieve protection against organophosphate (OP) poisoning. Trichostatin A (TSA), an inhibitor of histone deacetylase that de-condenses chromatin and increases the binding of transcription factors and mRNA synthesis, induced three- to four-fold extracellular and 8-10-fold intracellular AChE expression at the optimal dose of 165-333 nM in Neuro 2A cells. Pre-treatment with TSA protected against OP exposure. Thus, transcriptional inducers, such as TSA, up-regulate AChE, which then can scavenge the OP and protect the cells from OP-induced toxicity, and are potential novel ways to treat chemical warfare nerve agent (CWNA) exposure.
authors.affiliation: Division of Biochemistry, WRAIR, Silver Spring, MD 20910-7500, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Nambiar
authors.forename: B F
authors.initials: BF
authors.lastname: Curtin
authors.forename: Nabaneeta
authors.initials: N
authors.lastname: Pal
authors.forename: J R
authors.initials: JR
authors.lastname: Compton
authors.forename: B P
authors.initials: BP
authors.lastname: Doctor
authors.forename: R K
authors.initials: RK
authors.lastname: Gordon
mesh_terms: D000818:Animals; D002460:Cell Line; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D002802:Cholinesterases / Q000235:genetics* / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D002619:Chemical Warfare Agents; D006877:Hydroxamic Acids; C012589:trichostatin A; D002802:Cholinesterases