Reduction of neuropathy target esterase does not affect neuronal differentiation, but moderate expression induces neuronal differentiation in human neuroblastoma (SK-N-SH) cell line.
Neuropathy target esterase (NTE) is inhibited and aged by organophosphorus compounds that induce delayed neuropathy in human and some sensitive animals. NTE has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, to date, there is no direct evidence of the relevance of NTE in neurodifferentiation under physiological conditions. In this study, we have investigated a possible role for NTE in the all-trans retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of NTE by RNA interference indicated that reduction of NTE does not affect process outgrowth or differentiation of the cells, although moderate expression of NTE by expression of the NTE esterase domain accelerates the elongation of neurite processes. Mipafox, a neurotoxic organophosphate, was shown to block process outgrowth and differentiation in cells that have lowered NTE activity due to RNA interference, suggesting that mipafox may interact with other molecules to exert its effect in this context.
Chang
Ping-An
PA
Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, P.R. China.
Chen
Rui
R
Wu
Yi-Jun
YJ
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D020868:Gene Silencing; D006801:Humans; D007531:Isoflurophate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010261:Paraoxon / Q000378:metabolism / Q000494:pharmacology; D034622:RNA Interference; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; C005238:mipafox; D014212:Tretinoin; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; D010261:Paraoxon