Transcriptional induction of cholinesterase expression and protection against chemical warfare nerve agents.
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.
Nambiar
M P
MP
Division of Biochemistry, WRAIR, Silver Spring, MD 20910-7500, USA.
Curtin
B F
BF
Pal
Nabaneeta
N
Compton
J R
JR
Doctor
B P
BP
Gordon
R K
RK
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*
D002619:Chemical Warfare Agents; D006877:Hydroxamic Acids; C012589:trichostatin A; D002802:Cholinesterases