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Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line.

Abstract
Neuropathy target esterase (NTE) is phosphorylated and aged by oraganophosphorus compounds (OP) that induce delayed neuropathy in human and some animals. NTE has been proposed to play a role in neurite outgrowth and process elongation during neural differentiation. However, to date, there is no direct evidence of the relevance of NTE in neural differentiation under physiological conditions. In this study we have investigated a possible role for NTE in the all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells by antisense RNA. A NTE antisense RNA construct was generated and then transfected into human neuroblastoma SK-N-SH cells. A positive cell clone that can stably express NTE antisense RNA was obtained by G418 selection and then identified by western blotting. NTE activity was depressed in the transfected cells with only about 50% activity of the enzyme in the control cells. ATRA-induced differentiation of the neuroblastoma cells with lowered NTE activity revealed that inhibition of NTE expression does not affect neural differentiation in SK-N-SH cells. The result suggested that organophosphates may inhibit neural differentiation by initially acting on other targets other than NTE.
AuthorsPing-An Chang, Yi-Jun Wu, Rui Chen, Ming Li, Wei Li, Qi-Lian Qin
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 272 Issue 1-2 Pg. 47-54 (Apr 2005) ISSN: 0300-8177 [Print] Netherlands
PMID16010971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Organophosphates
  • RNA, Antisense
  • Tretinoin
  • Carboxylic Ester Hydrolases
  • neurotoxic esterase
Topics
  • Carboxylic Ester Hydrolases (antagonists & inhibitors, genetics, physiology)
  • Cell Differentiation (drug effects, physiology)
  • Cell Line, Tumor
  • Gene Expression (drug effects)
  • Humans
  • Nervous System Neoplasms (enzymology, genetics)
  • Neurites (drug effects, enzymology)
  • Neuroblastoma (enzymology, genetics)
  • Neurons (cytology, drug effects, enzymology)
  • Organophosphates (pharmacology)
  • RNA Interference
  • RNA, Antisense (genetics, pharmacology)
  • Transfection
  • Tretinoin (pharmacology)

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