Institute of Zoology, CAS, Beijing 100101, PR China.
Int J Toxicol. 2009 Sep-Oct;28(5):417-24. doi: 10.1177/1091581809340704. Epub 2009 Jul 20.
Neuropathy target esterase has been shown to be a lysophospholipase in mouse. The authors investigate the effect of neuropathy target esterase inhibition in mouse nervous tissues in vitro on the homeostasis of phosphatidylcholine and lysophosphatidylcholine by treating the homogenates with tri-ortho-cresyl phosphate, paraoxon, paraoxon plus mipafox, and phenylmethylsulfonyl fluoride. The activity of neuropathy target esterase is significantly inhibited by phenylmethylsulfonyl fluoride and paraoxon plus mipafox but not by paraoxon alone. Tri-ortho-cresyl phosphate slightly but significantly inhibits neuropathy target esterase activity in brain. The levels of phosphatidylcholine and lysophosphatidylcholine in all 3 nervous tissues are not obviously altered after treatment with tri-ortho-cresyl phosphate, paraoxon, or paraoxon plus mipafox. However, phosphatidylcholine and lysophosphatidylcholine levels are clearly enhanced by phenylmethylsulfonyl fluoride. It is concluded that inhibition of neuropathy target esterase in mouse nervous tissues is not enough to disrupt the homeostasis of phosphatidylcholine and lysophosphatidylcholine and that the upregulation by phenylmethylsulfonyl fluoride may be the consequence of combined inhibition of neuropathy target esterase and other phospholipases.
神经毒性靶酯酶在小鼠中已被证明是一种溶血磷脂酶。作者通过用三邻甲苯磷酸酯、对氧磷、对氧磷加米非司酮和苯甲基磺酰氟处理匀浆，研究了体外抑制小鼠神经组织中的神经毒性靶酯酶对磷脂酰胆碱和溶血磷脂酰胆碱的动态平衡的影响。苯甲基磺酰氟和对氧磷加米非司酮显著抑制神经毒性靶酯酶的活性，但对氧磷单独作用则不然。三邻甲苯磷酸酯轻微但显著抑制脑内的神经毒性靶酯酶活性。用三邻甲苯磷酸酯、对氧磷或对氧磷加米非司酮处理后，3 种神经组织中的磷脂酰胆碱和溶血磷脂酰胆碱水平均无明显改变。然而，苯甲基磺酰氟明显增强了磷脂酰胆碱和溶血磷脂酰胆碱的水平。结论是，抑制小鼠神经组织中的神经毒性靶酯酶不足以破坏磷脂酰胆碱和溶血磷脂酰胆碱的动态平衡，苯甲基磺酰氟的上调可能是神经毒性靶酯酶和其他磷脂酶联合抑制的结果。
