Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this work was to study the effects of chlorpyrifos (CPF) on the outgrowth of axons by differentiating mouse N2a neuroblastoma cells. This was achieved by morphological, Western blotting and enzymatic analyses of cells induced to differentiate in the presence and absence of CPF added either at the same time (co-differentiation) or 16 h after (post-differentiation) the induction of cell differentiation. The outgrowth of axon-like processes was impaired following 4 or 8 h exposure to CPF in both co- and post-differentiation experiments. Western blotting analysis revealed reduced levels of neurofilament heavy chain (NF-H) following 8 h of exposure but no significant effect at 4 h under both co- and post-differentiation conditions. By contrast, levels of the heat shock protein HSP-70 were raised at both time points, but only in co-differentiation experiments. Neuropathy target esterase (NTE) activity was lower than controls following 4 or 8 h of exposure under co-differentiation conditions, but not under any post-differentiation conditions. The results suggest that the inhibition of axon production and maintenance by CPF in differentiating N2a cells may involve multiple targets, which are different under co- and post-differentiation conditions.
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PMID:The toxicity of chlorpyrifos towards differentiating mouse N2a neuroblastoma cells. 1156 65

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.
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PMID:Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line. 1601 Sep 71

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.
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PMID:Reduction of neuropathy target esterase does not affect neuronal differentiation, but moderate expression induces neuronal differentiation in human neuroblastoma (SK-N-SH) cell line. 1612 34

Neuropathy target esterase (NTE), the human homologue of a protein required for brain development in Drosophila, is expressed primarily in neural cells but is also detected in non-neural cells. Although NTE has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation, the function of NTE has not been defined in neural cells. In this study we have investigated the possible role of NTE in neuroblastoma cells and non-neural cells using an over-expression strategy. Over-expression of NTE in human neuroblastoma SH-SY5Y cells and monkey kidney COS7 cells led to an accumulation of NTE on the cytoplasmic surface of the endoplasmic reticulum and inhibition of cell proliferation. In particular, high levels of NTE arrested COS7 cells at G2/M stage yet was not associated with arrest at a particular phase of the cell cycle in SH-SY5Y cells. Moreover, over-expression of NTE did not induce apoptosis in two kinds of cell lines as assessed by flow cytometry. These results suggest that the role of NTE over-expression in cell proliferation is associated with different mechanisms in different cells.
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PMID:Effect of over-expression of neuropathy target esterase on mammalian cell proliferation. 1698 44

Neuropathy target esterase (NTE) was originally identified as the primary target site of those organophosphorus compounds that induce delayed neuropathy in human and some animals. Here we examined the role of protein kinase C (PKC) in the regulation of the NTE activity in mammalian cells. Six-hour exposure of human neuroblastoma SK-N-SH cell to a PKC activator phorbol 12-myristate 13-acetate (PMA) decreased the activity of NTE, and this effect was blocked by the PKC inhibitor staurosporine. These results suggest that PKC down-regulates the activity of NTE. NTE protein levels were down-regulated by PMA-stimulation as detected by Western blot analysis using the NTE-specific antibody, which resulted from down-regulation of NTE mRNA level as verified by real-time reverse transcription polymerase chain reaction (RT-PCR). However, there were no changes in the activity or protein levels of stable expression of NTE esterase activity domain (NEST) in SK-N-SH cells and transient expression of full-length NTE construct in COS7 cells driven by cytomegalovirus (CMV) promoter rather than by the cell's own one, despite the absence or presence of PMA stimulation. Together, these findings suggest that stimulation with PMA reduces the expression of NTE mRNA levels but does not affect the exogenous promoter-driven NTE expression in mammalian cells.
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PMID:Down-regulation of neuropathy target esterase by protein kinase C activation with PMA stimulation. 1738 9