Neuronal differentiation of NTE-deficient embryonic stem cells.
Organophosphates induce neurological disorders. One of the enzymes inhibited by these compounds is neuropathy target esterase (NTE). In vitro, inhibition of NTE activity by organophosphates is correlated with inhibition of neurite initiation and reduction of neurite length, supporting the hypothesis that organophosphate-induced neurological disorders are caused by inhibition of NTE activity. However, there is no direct evidence for the involvement of NTE in organophosphate-induced impairment of neurites in vitro. To examine the role of NTE, we have generated NTE-deficient mouse embryonic stem cells. These cells can differentiate into neuron-like cells. Although NTE-deficient cells exhibited a delay in neurite initiation in vitro, both the proportion of neuron-like cells which initiated neurites and the elongation of these neurites occurred at the normal rate. These results demonstrate that NTE activity is not required for neurite initiation or elongation per se, but is essential for the optimal rate of neurite initiation.
Li
Zhongyou
Z
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Szurek
Paul F
PF
Jiang
Chuantao
C
Pao
Annie
A
Bundy
Brian
B
Le
Wei-dong
WD
Bradley
Allan
A
Yu
Y Eugene
YE
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D004781:Environmental Exposure / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000633:toxicity; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology
D009943:Organophosphorus Compounds; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase