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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the neurotoxin aluminum on markers of synaptic neurotransmission, adenosine 3',5'-monophosphate, and neurofilaments have been evaluated in a neuroblastoma x glioma hybridoma (NG108-15). Cells were exposed for 4 days to 2 mM aluminum lactate, a concentration that did not suppress growth. Compared to controls, the activity of choline acetyltransferase was significantly increased by 37% associated with an up-regulation in enzyme activity (Vmax). Muscarinic receptors, measured by [3H]QNB binding, were reduced by 41%. In contrast, the activities of acetylcholinesterase and glutamate decarboxylase were not significantly changed. Aluminum raised the level of cyclic AMP by 20%, although adenylate cyclase activity was unchanged. Small amounts of both phosphorylated and non-phosphorylated neurofilaments were detected in NG108-15 cells. Aluminum intoxication, however, did not alter the quantity, ultrastructure, or immunoreactivity of neurofilaments. Our results demonstrate the capability of aluminum to produce selected changes in cholinergic markers and levels of cyclic AMP in a rapidly dividing cell line.
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PMID:The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma x glioma hybridoma (NG108-15). 217 66

Inhibition of cell division and outgrowth of neurites with average rate of 31.5 +/- 4.4 micrometers per hour were observed in neuroblastoma cultures of the Neuro 2a clonal line 24 hours after the increase in the culture medium pH from 7.4 to 8.2. The total neurite length per one cell was about 298 +/- 36 micron in average by the 9-10th days of treatment. Simultaneously, a gradual enhancement of acetylcholinesterase cytochemical appearance took place attaining its maximum level by the same time. The peak sodium conductance, taken as a measure of sodium tetrodotoxin-sensitive potential-dependent channel density, was the same both in nondifferentiated cells grown in suspension or monolayer cultures, and in morphologically differentiated ones. The data lead to a conclusion that biochemical (acetylcholinesterase probe) and electrophysiological (sodium channel density) signs can express independently of morphological differentiation.
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PMID:[Acetylcholinesterase expression and changes in the electrical excitability of neuroblastoma cells during their morphological differentiation induced by an increase in the pH of the medium]. 245 61

Choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine metabolism, is expressed in a human cholinergic neuroblastoma cell line; MC-IXC. We demonstrate that ChAT activity is regulated in this cell line by cell density. It is believed that the mechanism of stimulation of enzyme activity involves cellular contact, as medium conditioned by cells of high density failed to mimic the effect of density alone, and trypsinization reversed this effect. Density did not increase acetylcholinesterase activity, another marker for the cholinergic phenotype, in MC-IXC cultures, demonstrating the independent regulation of these two cholinergic enzymes. Since increased density slows the rate of cell division, we used a DNA synthesis inhibitor to uncouple DNA replication from cell density. This had no effect on the specific activity of ChAT, suggesting that a cell-cell contact was the mediating factor. Other neuroblastoma cell lines were tested, and only cell lines which already contain ChAT activity were sensitive to its regulation by cell-cell contact, suggesting that cell-cell contact is permissive rather than instructive in this process. The effect of cell passage on ChAT activity is also discussed.
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PMID:Regulation of choline acetyltransferase activity by cell density in a cultured human neuroblastoma cell line. 246 20

We studied the effect of 5-aza-2'-deoxycytidine (5-AZA-CdR) on the differentiation of murine 41A3 neuroblastoma cells. Neuroblastoma cells treated with 0.1-1.0 microM 5-AZA-CdR underwent differentiation; markers of neuronal functions, such as acetylcholinesterase activity and growth of nerve fibers, were expressed at a higher level in the drug-treated cells than in the controls. This increased expression was accompanied by significant hypomethylation of newly synthesized DNA. A secondary event seemed to be a partial inhibition of DNA synthesis, cell proliferation and colony-forming activity. These effects were more pronounced than those caused by the related cytidine analog, 1-beta-D-arabinosil-cytosine (ARA-C). The results obtained suggest that 5-AZA-CdR may be an effective agent for the growth control of human neuroblastoma cells.
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PMID:5-Aza-2'-deoxycytidine as inducer of differentiation and growth inhibition in mouse neuroblastoma cells. 247 29

The N-myc cellular oncogene is frequently amplified and expressed at a high level in neuroectodermal tumor cells such as neuroblastoma and retinoblastoma. We examined N-myc expression in NCB-20 hybrid (N18TG2 neuroblastoma x embryonic Chinese Hamster brain) cells. After five days of culture, cells treated with 1 mM db cAMP show extensive neurite outgrowth and secrete acetylcholinesterase into the media at a level three times higher than untreated control. In situ hybridizations, dot blots, and Northern analyses reveal four- to eight-fold higher levels of N-myc mRNA in the treated, differentiated cells than in the untreated, undifferentiated controls. Our results show that the highly differentiated state is not incompatible with a high level of N-myc mRNA.
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PMID:Increased N-myc mRNA expression associated with dibutyryl cyclic AMP induced neuroblastoma differentiation. 256 Apr 82

Differentiation in the mouse neuroblastoma cells is induced by cAMP and is characterized by neurite extension and increased acetylcholinesterase, cAMP-phosphodiesterase, and RI cAMP-binding activities. To gain a better understanding of the regulation of expression and the possible function of the RI cAMP-binding protein in neuroblastoma cell differentiation, we evaluate the specificity of action of cAMP analogues and agents that increased intracellular cAMP concentration in the induction of the 47,000-dalton RI protein. The amount of RI in cell extracts was quantitated by the photoactivated incorporation of 8-N3-[32P]cAMP into the 47,000-dalton RI and by ELISA and Western blot techniques. Our results showed that dibutyryl cAMP, forskolin, prostaglandin E1, 3-isobutyl-1-methyl xanthine, and papavarine gave a 2- to 4-fold increase in the RI cAMP-binding protein coincident with the expression of various morphological and biochemical differentiation phenotypes in the mouse neuroblastoma cells. However, the effects of 8-bromo-cAMP were different. 8-Bromo-cAMP effectively promoted neurite extension and increased acetylcholinesterase and cAMP-phosphodiesterase activities; however, there was no concomitant increase in the RI cAMP-binding protein. The result raises interesting questions concerning the coupling of expression of the various differentiation phenotypes in the mouse neuroblastoma cells.
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PMID:Specificity of the action of cAMP agonists in the induction of RI cAMP-binding protein in mouse neuroblastoma cells. 283 19

A latent state of the herpes simplex virus type 2 genome was established in a human neuroblastoma cell line (SMS-KCNR) to initiate studies on the mechanism by which host cells interact and regulate latent viral genes. To establish viral latency, it was necessary to prevent virus replication by briefly exposing the infected cells to antiherpetic acycloguanosine (20 microM) and human interferon (120 U/ml). Subsequently however, these cells could be propagated without any antiherpetic agents and almost 60% of the cell population contained viral genome. While these cells did not produce any infectious virus, immunoblot analysis revealed two intracellular polypeptides with molecular weights of 87.5 kDa and 67 kDa, respectively, that interacted with hyperimmune anti-HSV2 rabbit serum. Two cellular enzymes, acetylcholinesterase and choline acetyltransferase, involved in metabolism of neurotransmitters were expressed at a higher level in the latently infected cells than in the mock-infected control cells. Infectious HSV-2 could be reactivated from these cells only after the cells had undergone massive morphological differentiation and maturation to flat cell types by extensive treatment with 20 micron bromodeoxyuridine.
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PMID:Regulation of viral and cellular genes in a human neuroblastoma cell line latently infected with herpes simplex virus type 2. 283 26

Morphological and biochemical parameters of neuroblastoma differentiation were assessed in 12 clonal derivatives of the N-18 mouse neuroblastoma cell line selected for their ouabain-resistant (ouar) property. When cultured in a normal growth medium, nine of the 12 ouar cell lines exhibited a more complex pattern of neurite outgrowth than the parental N-18 cells. The morphological pattern most frequently observed with the ouar cells was the extension of several branched processes per cell. This pattern of spontaneous neurite outgrowth in the ouar cell lines can be correlated with an increase in expression of the 47,000-dalton RI cyclic AMP (cAMP)-binding protein. The growth rate, intracellular level of cAMP, and acetylcholinesterase activity of the ouar cell lines were not significantly different from those of the parental N-18 neuroblastoma cells. Treatment of the parental and ouar neuroblastoma cell lines with 1 mM N6, O2-dibutyryl cAMP promoted an elaborate pattern of neurite outgrowth and marked increases in acetylcholinesterase and RI cAMP-binding activities. The distinctive pattern of differentiation phenotype exhibited by the ouar cells and the dibutyryl cAMP-induced differentiated neuroblastoma cell suggests that these two protocols yielded different degrees of differentiation. Furthermore, our results suggest a linkage of the biochemical events underlying ouabain resistance and expression of differentiation phenotypes in the mouse neuroblastoma cells.
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PMID:Neurite extension and increased expression of RI cyclic AMP-binding protein in ouabain-resistant neuroblastoma mutants. 284 59

We have compared the effects of forskolin, N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP, Bt2-cAMP), and butyrate on several aspects of neuroblastoma cell physiology. The morphology of Neuro 2A cells was similar after incubation with forskolin and Bt2-cAMP, which caused extensive neurite outgrowth, whereas in the presence of butyrate some rudimentary neurites were formed but they were not nearly as extensive. All compounds produced a dose-dependent inhibition of cell proliferation, but the effect of Bt2-cAMP was more marked than that caused by forskolin, thus showing that the effect of Bt2-cAMP is due partially to the butyrate released. Acetylcholinesterase activity was lower in the cells incubated with butyrate or Bt2-cAMP than in untreated cells or in forskolin-treated cells. This suggests that cyclic AMP does not play a role in the regulation of this enzyme. Bt2-cAMP produced histone acetylation, a well-known effect of butyrate in cultured cells, whereas forskolin did not affect this modification. Consequently, the levels of thyroid hormone receptor, a nuclear protein whose concentration is regulated by butyrate through changes in acetylation of chromatin proteins, were decreased in cells incubated with Bt2-cAMP or butyrate, but were unaffected by forskolin. Butyrate elevated the concentration of histone H1(0), a protein that increases in neuroblastoma cells as a result of different treatments that block cell division. The concentration of H1(0) in the cells treated with Bt2-cAMP was at a level intermediate between that found after treatment with butyrate and with forskolin. The present results clearly indicate that some of the effects of Bt2-cAMP on neuroblastoma cells can be attributed to the butyryl moiety of this compound rather than to the cyclic nucleotide itself.
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PMID:Comparison of the effects of forskolin and dibutyryl cyclic AMP in neuroblastoma cells: evidence that some of the actions of dibutyryl cyclic AMP are mediated by butyrate. 284 86

Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 microM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an IC50 of 450 microM. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki value of 162 microM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1-stimulated [3H]cyclic AMP formation was not affected. The Ki for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 microM. Caracemide was a competitive inhibitor of acetylcholinesterase with a Ki value of 8 microM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E-115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system.
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PMID:Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115). 287 11


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