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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stability of a clonal mouse neuroblastoma x rat glioma hybrid cell line was examined. Cell volume and cellular content of DNA and protein were measured as functions of the passage number. They decreased with the number of serial subcultivations. Cellular volume was linearly related to cellular DNA and protein. Thus, measurements of cell volume can be used to monitor the loss of DNA from hybrid cells. After about 60 passages a stable population of hybrid cells arose, as judged by the constancy of cellular volume and by the decreased coefficient of variation of the cell volume distribution. A mathematical model for the kinetics of the simultaneous loss of cellular volume, DNA and protein is introduced. Several neuronal properties were investigated. The specific activity of the neurotransmitter enzyme choline acetyltransferase decreased by more than 50% during 56 passages. After 70 subcultivations, the hybrid cells were still capable of extending processes, action potentials could still be elicited electrically or by iontophoretic application of acetylcholine, and the cells still responded to prostaglandin E1 as they do at low passage number.
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PMID:Influence of the time in culture on cellular and neuronal properties of neuroblastoma x glioma hybrid cells. With an appendix, mathematical description of the kinetics of the loss in cell volume. 59 72

Neuroblastoma x glioma hybrid NG108-15 cells and mouse neuroblastoma N18TG-2 and N1E-115 cells were transiently transfected with the sense cDNA coding for rat choline acetyltransferase (ChAT). All transfected cell lines showed a high level of ChAT activity. ACh secretion was monitored by recording miniature end-plate potentials (MEPPs) in striated muscle cells that had been co-cultured with transfected cells. The number of muscle cells with synaptic responses and the MEPP frequency were higher in co-culture with transfected NG108-15 cells than with control or mock cells. No synaptic response was detected in muscle cells co-cultured with transfected N18TG-2 or N1E-115 cells. The results show that ACh secretion into the synaptic cleft was enhanced due to ChAT overexpression in NG108-15 hybrid cells but not in neuroblastoma cells.
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PMID:Enhanced acetylcholine secretion in neuroblastoma x glioma hybrid NG108-15 cells transfected with rat choline acetyltransferase cDNA. 146 77

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

It is known that nerve growth factor (NGF) induces neurite outgrowth and elevation of the activity of adrenergic marker enzyme, tyrosine hydroxylase (TH) in clonal rat pheochromocytoma cells (PC12), whereas glioma-conditioned medium (GCM) induces neurite outgrowth and elevation of the activity of cholinergic marker enzyme, choline acetyltransferase (ChAT) in PC12 cells. In the previous study we have shown that retinoic acid (RA) induces specific elevation of ChAT activity and depression of TH activity without morphological differentiation (Matsuoka, I. et al., Brain Res., 502 (1989]. In the present study, we compared the effects of NGF, GCM and RA on the intracellular signalings in PC12 cells in relation to the mechanism of cholinergic differentiation. Addition of NGF, GCM or RA to the culture medium of PC12 cells caused a rapid rise in intracellular Ca2+ concentration [( Ca2+]i) reaching the level of almost 2.5-fold the resting condition within 3-18 h. Thereafter, [Ca2+]i of NGF-treated cells were decreased to the resting level within 12 h. On the other hand, [Ca2+]i of GCM-and RA-treated cells decreased to a level which was 1.8- to 2-fold the resting condition within 24-48 h and stayed at this level for up to 4-7 days. When homogenates of GCM- and RA-treated PC12 cells were incubated with [gamma-32P]ATP, phosphorylation of a protein with molecular mass of 27 kDa (27 K-protein) was specifically enhanced. The phosphorylation of the 27 K-protein was not seen in the homogenate of the NGF-treated cells. The phosphorylation of the 27 K-protein was dependent on Ca2+ and inhibited by inhibitors of Ca2+-dependent protein kinase, H-7 and W-7. Addition of H-7 and W-7 to the culture medium of PC12 cells abolished the elevation of ChAT activity specifically induced by GCM and RA. These observations suggested that the sustained increase of [Ca2+]i and Ca2+-dependent protein phosphorylation are involved in the intracellular signaling mechanism required for the cholinergic differentiation of PC12 cells induced by GCM and RA.
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PMID:Possible involvements of intracellular Ca2+ and Ca2+ -dependent protein phosphorylation in cholinergic differentiation of clonal rat pheochromocytoma cells (PC12) induced by glioma-conditioned medium and retinoic acid. 258

This study was designed to establish an in vitro model with biochemical and morphological similarities to the human neurodegenerative disease GM1 gangliosidosis. Utilizing a specific inactivator of the lysosomal enzyme GM1-ganglioside beta-galactosidase (beta-D-galactopyranosylmethyl-p-nitrophenyltriazene [beta-GalMNT]) and neuroblastoma X glioma hybrid cells (NG108-15), we suppressed beta-galactosidase activity for up to 72 hours. Coincidental with suppression of this enzyme to levels less than 1% of control, we found up to a nine-fold accumulation of its substrate, the GM1-ganglioside, and the ultrastructural appearance of membranous cytoplasmic bodies. beta-GalMNT treatment suppressed growth but had little effect on the specific activity of choline acetyltransferase, lactate dehydrogenase, or other lysosomal enzymes including galactosylceramidase. This model should permit studies of the neurophysiological effects of increased ganglioside accumulation and their reversibility.
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PMID:Inactivation of GM1-ganglioside beta-galactosidase by a specific inhibitor: a model for ganglioside storage disease. 303 98

The effects of anticonvulsants on markers of growth, intracellular enzymes, and synaptic functions were evaluated using a rapidly dividing cholinergic neuroblastoma x glioma hybrid cell-line (NG108-15). Cell cultures were exposed for 4 days to phenobarbital, phenytoin, carbamazepine, or valproic acid. Anticonvulsant concentrations added to the media were selected to produce free levels in the cell media that were equivalent to free levels in humans ranging from therapeutic to very toxic. Free levels of anticonvulsants in the toxic range affected cell number, protein content, and neurochemical markers. However, only valproic acid and phenytoin reduced cell growth at therapeutic free drug concentrations. Valproic acid was the only medication to act as a differentiating agent, significantly increasing the activity of choline acetyltransferase, beta-galactosidase, and muscarinic cholinergic receptor binding. These results emphasize the importance of performing drug studies at appropriate free drug concentrations and suggest that valproic acid differs from other commonly prescribed anticonvulsants by having both a growth-suppressing and a differentiating effect.
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PMID:Effects of anticonvulsants on cell growth and enzymatic and receptor binding activity in a neuroblastoma x glioma hybrid cell culture. 310 72

When nerve-growth factor (NGF) was added to 17-day fetal rat central nervous system (CNS) septal neurons in culture using a defined medium, choline acetyltransferase (ChAT) activity was greatly induced. However, glioma-conditioned medium (GCM), which is expected to contain cholinergic neurotrophic factor(s) different from NGF, did not affect the ChAT activity of the cultured septal neurons. On the contrary, ChAT activity of 19-day fetal rat hippocampal neurons in culture was increased by the addition of GCM but not by NGF. These phenomena were confirmed in septal and hippocampal neuronal cultures obtained from the same embryonic day, i.e., 18-day fetal rat. The NGF-mediated increase in ChAT activity of cultured septal neurons was culture-time dependent (2.3-fold increase after 3 and 3.5-fold increase after 6 days in culture) and NGF-dose dependent (the ED50 value was 0.8 ng/ml). The effect of NGF was completely abolished by the addition of specific anti-NGF antibodies. The differential effects of NGF and GCM on several other cultured cholinergic neurons from 17-day fetal rat spinal cord, striatum, brainstem and amygdala were measured. NGF tended to increase ChAT activities of cultured striatal and amygdala neurons but not cultured spinal cord and brainstem neurons. GCM increased ChAT activities in the latter two cultures, while having no effect on the former cultures. Although the extent of increase of NGF-mediated ChAT activities of cultured striatal and amygdala neurons were low, NGF-mediated increase of the striatal ChAT activity showed the pattern resembling that of cultured septal neurons as to time-course, dose-dependency and anti-NGF antibody sensitivity. NGF did not affect the tyrosine hydroxylase activity in the cultured brainstem catecholaminergic neurons.
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PMID:Differential effects of nerve-growth factor and glioma-conditioned medium on neurons cultured from various regions of fetal rat central nervous system. 377 32

Ethylcholine mustard aziridinium ion (AF64A, MEChMAz) has been proposed as a cholinergic neuron-specific neurotoxin. We report that in further studies on its mechanism of action incubation of the cholinergic neuroblastoma X glioma cell line, NG-108-15, with 100 microM AF64A resulted in a rapid decrease in cellular choline acetyltransferase (ChAT) activity which preceded cytotoxicity. Thus, a 60-85% decrease in ChAT activity was measured within 5 h of AF64A exposure, whereas cell lysis (measured as the release of the cytosolic enzyme lactate dehydrogenase into the medium) did not become apparent until 18 h of AF64A exposure. This led us to examine the effects of AF64A on partially purified ChAT. We report a concentration- and time-dependent inhibition of partially purified ChAT by AF64A that could not be reversed by dialysis but could be prevented by coincubation of the enzyme and AF64A with choline but not with acetyl-coenzyme A. We present kinetic evidence that choline and AF64A compete for the same site on the enzyme. In addition, thiosulfate, which inactivates the aziridinium ion, eliminated AF64A's capacity to inhibit the enzyme. AF64A also irreversibly inhibited partially purified choline kinase and acetylcholinesterase but not lactate dehydrogenase, alcohol dehydrogenase, carboxypeptidase A, or chymotrypsinogen, enzymes that do not use choline as a substrate or product. Thus, the data suggest that AF64A acts as an irreversible active site directed inhibitor of ChAT and possibly other enzymes recognizing choline.
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PMID:AF64A: an active site directed irreversible inhibitor of choline acetyltransferase. 383 98

Culture medium conditioned over C6 glioma cells (GCM) contains factors which induce neurite outgrowth from clonal rat pheochromocytoma (PC12) cells. The effects of GCM on the cell-substratum adhesion of PC12 cells, which is an early event required for the neurite outgrowth, were investigated. The results obtained are as follows. Addition of GCM promoted the adhesion of PC12 cells specifically to collagen-coated tissue culture dish. The GCM-promoted adhesion of PC12 cells was prevented by the treatment of the cells with cytochalasin B, concanavalin A and glycosidase mixture suggesting the contribution of microfilaments and cell surface carbohydrates in the cell adhesion. GCM did not increase significantly the intracellular content of cAMP and the extent of cell adhesion promoted by cAMP or dibutyryl-cAMP was much less than that by GCM. Two active factors contained in GCM were separated by either gel filtration or chromatofocusing using the cell adhesion assay as an index. The first factor with an apparent mol. wt. around 40,000 had the abilities to induce the neurite outgrowth and to enhance the choline acetyltransferase activity in addition to the ability to promote the adhesion of PC12 cells. The second factor with an apparent mol. wt. around 10,000 was devoid of the ability to induce the neurite outgrowth, but had the abilities to enhance the choline acetyltransferase activity and to promote the adhesion of PC12 cells. Both factors were sensitive to trypsin digestion and relatively heat stable. The significance of these factors in the neuronal differentiation was discussed.
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PMID:Promotion of cell-substratum adhesion of clonal rat pheochromocytoma cells (PC12) by factors contained in glioma-conditioned medium (GCM): separation of two active factors contained in GCM. 394 4

A new hybrid cell line, designated NG115-401, produced a significant amount of immunoreactive (IR) substance P-like material. The production was measured by radioimmunoassay using specific antisera raised to substance P. The production rate was dependent upon cell growth, and maximum production occurred at the same stage (late logarithmic stage) as the time of appearance of choline acetyltransferase activity, one of the characteristic neuronal properties of the cells. On the other hand, no IR-substance P was found in hybrid cells other than NG115-401, i.e. NG115-301 and NG115-303 cells, which were derived from the same parent mouse neuroblastoma N115TG-2 cells. Furthermore, in an attempt to survey IR-substance P production in several clonal cells, consisting of some mouse neuroblastoma cells and a rat glioma cell, and several of their hybrid cells, we could find no cell line producing a significant amount of IR-substance P except for NG115-401 hybrid cells. The cellular production of IR-substance P in NG115-401 hybrid cells was also confirmed by detecting the material in all 14 subpopulations of this hybrid cells. Partial characterization of IR-substance P-like material produced by NG115-401 hybrid cells was carried out by its application to gel-filtration column chromatography. Only high molecular weight material (approximately 26,000) appeared in the column eluates.
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PMID:A mouse neuroblastoma x rat glioma hybrid cell produces immunoreactive substance P-like material. 616 18


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