Transcriptional induction of cholinesterase expression and protection against chemical warfare nerve agents

Autor: M P, Nambiar, B F, Curtin, Nabaneeta, Pal, J R, Compton, B P, Doctor, R K, Gordon
Rok vydání: 2006
Předmět:
Zdroj: Chemico-biological interactions.
ISSN: 0009-2797
Popis: 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.
Databáze: OpenAIRE