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 primary interaction of tetanus toxin and toxoid with mouse neuroblastoma cells (C 1300, clone NB2A) in tissue culture was studied using direct immunofluorescence. Experiments were done in standard routine cultures and also those influenced by chemical modulators. There is a difference in the characteristic binding response between the growth culture cells (grown in presence of fetal calf serum) and differentiating culture cells (grown in absence of serum). Exposure to the toxin gives no visible effect on the cell division or viability in growth cultures; whereas in differentiating cells the processes are shortened and the adherence to the glass is diminished without involving significant cell death. The toxoid did not bind at all under the same experimental conditions. Since there was no biological effect in growth cultures we have called this binding ineffective, and in the case of the differentiating cells, effective binding. Stimulation of pinocytosis increases the uptake of toxin in both cultures. Presence of some surface bound toxin still remaining on the differentiating cells indicates the possibility of another sort of mechanism for internalization. Pre-treatment of the cells with neuraminidase or beta-galactosidase to alter the membrane gangliosides eliminates binding in growth cultures but not in differentiating cultures. From these results we suggest that even though the toxin may well bind to gangliosides, at least in the differentiating cultures they are not solely responsible for the fixation. The morphologically observed effective binding is probably that not related to gangliosides.
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PMID:Interaction of tetanus toxin and toxoid with cultured neuroblastoma cells. Analysis by immunofluorescence. 32 Apr 89

Among the potential uses of defective herpes simplex virus (HSV-1) vectors are to study neuronal physiology, neuronal gene regulation, and to perform gene therapy of neuronal diseases. The prototype HSV-1 vector, pHSVlac, stably expresses Escherichia coli beta-galactosidase from the HSV-1 immediate early (IE) 4/5 promoter in cultured rat peripheral and CNS neurons, and in neurons in the adult rat brain. The LacZ gene and the IE 4/5 promoter in pHSVlac can be replaced with genes which affect neuronal physiology or cellular promoters, respectively. A system is required to characterize these HSV-1 vectors; cultured neurons, a mixture of different kinds of neurons and glia, cannot be used. In contrast, neural cell lines represent a homogenous population of neural cells available in virtually unlimited quantities. A system, using neural cell lines, to characterize HSV-1 vectors carrying other genes or promoters is now reported: First, 4 assays are described to detect HSV-1 vector DNA, RNA transcribed from the vector, and to quantitate beta-galactosidase expression. Second, 8 cell lines derived from rodents, primates, and humans were infected with pHSVlac virus and shown to express beta-galactosidase. The cell lines tested included adrenergic and cholinergic mouse neuroblastoma cells, rat pheochromocytoma cells, rodent pituicytes, and human neuroblastoma cells. Infection of these cell lines should prove useful for characterizing HSV-1 vectors with molecular and biochemical assays. Third, differentiated rat pheochromocytoma and mouse neuroblastoma cells, which resemble neurons, were infected with pHSVlac virus and shown to stably express beta-galactosidase. Infection of these cells should be useful for determining the effect of various HSV-1 vectors on neuronal physiology. Thus, HSV-1 vectors containing various genes or promoters can be characterized using the system described in this study.
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PMID:A system, using neural cell lines, to characterize HSV-1 vectors containing genes which affect neuronal physiology, or neuronal promoters. 164 53

Expression of the c-fos protooncogene is induced by a great variety of extracellular stimuli. A fos-lacZ fusion gene has been constructed that recapitulates this regulation. The fos-lacZ gene was introduced into B104 neuroblastoma cells for use in a quantitative assay for stimulus-transcription coupling. Both alpha- and beta-adrenergic agonists, dibutyryl cAMP, and phorbol ester induced beta-galactosidase activity in a dose-dependent manner. Thus, the interactions of receptors with agonists and antagonists, as well as intracellular second messenger-mediated signaling events, can be analyzed quantitatively. This approach represents a prototypic method for investigating stimulus-response coupling based upon gene expression.
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PMID:Regulation of a fos-lacZ fusion gene: a paradigm for quantitative analysis of stimulus-transcription coupling. 164 27

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

Opiate receptor binding decayed exponentially in mouse neuroblastoma-rat glioma (NG108-15) hybrid cell preparations following exposure to increasing doses of ionizing radiation (0.2 to 7.0 Mrads; 2.0 Mrads/min). Target size analysis revealed that [3H][D-Ala2, D-Leu5]enkephalin (agonist) and [3H]naloxone (antagonist) bound specifically to a component with an apparent molecular size of 200,000 +/- 20,000. Lyophilization of cells for the irradiation procedure did not significantly alter receptor affinity or binding capacity for these ligands. Furthermore, the loss of opiate receptor binding in irradiated cell samples could not be attributed to reduced receptor affinity since increasing concentrations of radiolabeled ligand failed to reverse the inhibition; nonspecific binding decreased only slightly under identical experimental conditions. The value of determining molecular size by radiation inactivation analysis was confirmed by showing that apparent target sizes for two representative lysosomal enzymes (beta-galactosidase and alpha-mannosidase) were consistent with results obtained previously using conventional methods. Thus, the data suggest that the ligand binding component of delta-opiate (enkephalin) receptors in NG108-15 cells has a minimum functional size of approximately 200,000.
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PMID:Molecular size of opiate (enkephalin) receptors in neuroblastoma-glioma hybrid cells as determined by radiation inactivation analysis. 629 28

Rat glioma X mouse neuroblastoma hybrid neurotumor cells (NG108-15), synchronized by amino acid deprivation, showed a cell-cycle-dependent peak of activity of a ganglioside N-acetylgalactosaminyl transferase 14-24 h following release from the cell cycle block (S/G2 phase). Maximal expression of two typical lysosomal hydrolases, N-acetyl-beta-hexosaminidase and beta-galactosidase, occurred between 18 and 21 h following release (S phase), declining to G1 phase levels during the peak of N-acetylgalactosamine (GalNAc) transferase activity. In addition, glycosyltransferase activity in G2 phase cells showed an increase in apparent Vmax (suggesting the presence of more enzyme/mg of cell protein) and apparent binding affinity for uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) (32 versus 14 microM) when compared to transferase activity in the G1 phase. However, the opioid peptide enkephalin [D-Ala2, D-Leu5], which inhibits ganglioside GalNAc transferase activity in unsynchronized NG108-15 cultures, was much more inhibitory in whole cells 8 h after release from the cell cycle block (G1 phase) than in cells 20 h after release (G2 phase), with 50% inhibition occurring at 2 X 10(-9) M and 2 X 10(-7) M, respectively. These results suggest that the GalNAc transferase activity is regulated in more than one way during the cell cycle, since both Vmax and Km changes are observed, and that the cyclic AMP-dependent mechanism by which opiates reduce transferase activity is receptor mediated and cell cycle dependent.
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PMID:Cell-cycle dependence of a ganglioside glycosyltransferase activity and its inhibition by enkephalin in a neurotumor cell line. 642

During herpes simplex virus latency, transcripts accumulate from a single transcription unit of the viral genome. The promoter for these latency-associated transcripts (LAT) has been located, and a number of studies have documented the specific regions of this promoter which are important in transient assays of neuronal cells in culture. To examine the regulation of this promoter from the viral genome, both in vitro and in vivo, a series of seven promoter deletion viruses which drive the expression of the reporter gene beta-galactosidase was constructed. Rabbit skin cells were infected in cell culture with viruses bearing each promoter mutation, and the LAT promoter activity was compared with that obtained by infecting two neuronal cell lines, ND7 cells and C1300 neuroblastoma cells. Mouse dorsal root ganglia were also infected with these recombinant viruses by footpad inoculations, and beta-galactosidase activity was measured. Infected neuronal cells lines and dorsal root ganglia exhibit much more LAT promoter activity than infected rabbit skin cells, suggesting that the region upstream of -250 may contain one or several neuronal specific DNA-binding sites. However, a comparison of LAT promoter activities within the deletion series revealed many differences between neurons of the dorsal root ganglia infected in vivo and the two neuronal cell lines infected in vitro. These results suggest that neurons may vary extensively in the quantity or kind of transcription factors they contain.
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PMID:In vivo deletion analysis of the herpes simplex virus type 1 latency-associated transcript promoter. 788 73

This study used reporter gene constructs containing regulatory regions of the c-fos, vasoactive intestinal peptide, and choline acetyltransferase genes to determine the role of p21ras and protein kinase C in the action of ciliary neurotrophic factor and leukemia inhibitory factor. Down-regulation of protein kinase C with phorbol ester did not affect the induction of either c-fos-beta-galactosidase or vasoactive intestinal peptide-luciferase by ciliary neurotrophic factor or leukemia inhibitory factor. In contrast, while leukemia inhibitory factor induction of choline acetyltransferase-luciferase expression was protein kinase C-independent, there appears to be both protein kinase C-dependent and -independent pathways for induction of choline acetyltransferase-luciferase by ciliary neurotrophic factor. Cotransfection of a dominant-negative mutant p21rasN17 blocked nerve growth factor-mediated induction of c-fos-beta-galactosidase, but did not affect induction of c-fos-beta-galactosidase, vasoactive intestinal peptide-luciferase, or choline acetyltransferase-luciferase by either ciliary neurotrophic factor or leukemia inhibitory factor. Thus, in contrast to the action of nerve growth factor, gene induction by ciliary neurotrophic factor, and leukemia inhibitory factor is ras-independent in IMR-32 neuroblastoma cells.
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PMID:Differential requirements for p21ras and protein kinase C in the regulation of neuronal gene expression by nerve growth factor and neurokines. 803 40

The toxic effects of two metabolic inhibitors, dinitrophenol and iodoacetic acid, were compared. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed to different concentrations of the toxic compounds for 24, 48 and 72 h to study basal toxicity effects (cell proliferation by quantification of total protein content (PR) and relative neutral red uptake (RNRU) by lysosomes). The following biochemical indicators assessed in the in vitro test system were: cytosolic phosphofructokinase (PFK) and enolase (ENL) activities in glycolysis; mitochondrial succinate dehydrogenase (SDH) activity in the citric acid cycle; lysosomal beta-galactosidase (GAL) activity; and neuronal acetylcholinesterase (AChE) activity. The effects of the two metabolic inhibitors on the various indicators differed. Iodoacetic acid was found to be far more toxic than dinitrophenol to neuroblastoma cell proliferation at 24 h exposure. Though 2,4-dinitrophenol and iodoacetic acid both inhibited cell proliferation of the neuroblastoma cells, their effects on the other endpoints were opposite. Dinitrophenol was a general activator of the metabolism, particularly affecting lysosomal function. Iodoacetic acid did not significantly alter general metabolism, but considerably modified lysosomal function and AChE activity. The modification of lysosomal function of Neuro-2a cells by the two compounds was quite different: dinitrophenol increased RNRU and GAL activity, and iodoacetic acid decreased both parameters.
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PMID:Comparative effects of the metabolic inhibitors 2,4-dinitrophenol and iodoacetate on mouse neuroblastoma cells in vitro. 865 53


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