Effect of Inhibition of Neuropathy Target Esterase in Mouse Nervous Tissues In Vitro on Phosphatidylcholine and Lysophosphatidylcholine Homeostasis

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.