Nambiar M P, Curtin B F, Pal Nabaneeta, Compton J R, Doctor B P, Gordon R K
Division of Biochemistry, WRAIR, Silver Spring, MD 20910-7500, USA.
Chem Biol Interact. 2005 Dec 15;157-158:409-10. doi: 10.1016/j.cbi.2005.10.079.
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.
我们研究了转录诱导剂是否能增强细胞系中乙酰胆碱酯酶（AChE）的表达，以实现对有机磷酸酯（OP）中毒的保护作用。曲古抑菌素A（TSA）是一种组蛋白脱乙酰酶抑制剂，可使染色质解聚并增加转录因子的结合及mRNA合成，在Neuro 2A细胞中，其最佳剂量为165 - 333 nM时，可诱导细胞外AChE表达增加三到四倍，细胞内增加8 - 10倍。TSA预处理可预防OP暴露。因此，像TSA这样的转录诱导剂可上调AChE，进而清除OP并保护细胞免受OP诱导的毒性，是治疗化学战神经毒剂（CWNA）暴露的潜在新方法。
