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)

Attachment and neurite extension processes have been evaluated for an immortalized derivative cell of a rat dorsal root neuron after fusion with a mouse neuroblastoma cell (the clonal F11 hybrid cell line) and these processes compared with previous studies of neuroblastoma cells, since both cell types may be derived from the neural crest of the developing embryo. Biochemically defined substrata were provided by human plasma fibronectin (pFN), the heparan sulfate-binding protein platelet factor-4 (PF4), and the ganglioside GM1-binding protein cholera toxin B subunit (CTB). While some attachment of unsupplemented cells was noted on CTB substrata, GM1 supplementation permitted F11 cells to attach as well on CTB as on pFN or PF4. On PF4, very few neurite processes were observed while on pFN two morphologically distinct types of neurites could be identified: short, linear processes in a low percentage of cells resembling those of neuroblastoma cells and long, irregular and narrow processes in a higher percentage of cells resembling those of dorsal root neurons. On CTB, neurites of the latter class were even more prominent; however, cell bodies on CTB failed to spread by cytoplasmic extension as commonly observed in F11 cells on pFN and, to some extent, on PF4. The formation of both neurite classes on either pFN or CTB was completely inhibited by low concentrations of an RGDS (Arg-Gly-Asp-Ser) peptide in the medium of cultures, indicating the significance of pFN's binding to cell surface integrin or ganglioside GM1's possible interaction with integrin for mediating the differentiative process. In contrast, neurite formation of neuroblastoma cells is refractile to the soluble peptide as reported previously. Neurite extensions of F11 cells on either pFN or CTB were comparably sensitive to low concentrations of cytochalasin D, revealing the mediation of microfilament reorganization in these processes. Treatment of F11 cells with cycloheximide failed to inhibit neurite extension on pFN but did partially inhibit extension on CTB; this contrasts with the very high sensitivity of neurite formation by neuroblastoma cells on CTB substrata reported previously.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple and alternative adhesive responses on defined substrata of an immortalized dorsal root neuron hybrid cell line. 316 39

A procedure is described for assay of GM1 and other gangliotetraose-type gangliosides at the picomole level. The gangliosides are absorbed onto polystyrene microwells and treated with neuraminidase and then with cholera toxin B subunits conjugated to horseradish peroxidase. Color is developed and quantified spectrophotometrically. Omission of neuraminidase gives a measure of GM1 alone. Linearity was obtained between 0.5 and 3 pmol. This procedure was applied to ganglioside mixtures isolated fron neuro-2A neuroblastoma and PC12 pheochromocytoma cells. For the latter, an additional step involving reaction with fucosidase increased the yield of GM1 due to the presence of fucosylated gangliosides. Application of the same reagents as a TLC overlay procedure to the gangliosides from neuro-2A cells revealed the presence of GD1a, GD1b, and GT1b in addition to GM1, thus confirming the presence of a family of gangliotetraose gangliosides.
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PMID:Quantification of gangliotetraose gangliosides with cholera toxin. 318 15

The oligosaccharide portion of ganglioside GM1 was found to enhance neuritogenesis by S20Y murine neuroblastoma cells grown in vitro. The average length of the neurites produced by cells grown in the presence of the oligosaccharide portion of GM1 was comparable to that of cells grown in the presence of intact GM1. The processes of these cells were significantly longer (p less than 0.005, pooled t test) than those of cells grown in the presence of comparable concentrations of sialic acid, lactose, sialyllactose, GD1a, or the oligosaccharide moiety of GD1a. These results suggest that it is the oligosaccharide portion of GM1 that is responsible for the ability of GM1 to enhance process outgrowth by S20Y neuroblastoma cells.
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PMID:Oligosaccharide portion of GM1 enhances process formation by S20Y neuroblastoma cells. 337 8

The 4 major ganglioside species, GM1, GD1a, GD1b and GT1b (200 micrograms/ml), were tested individually for the ability to stimulate neuronal trophic responses. The growth parameters measured were: morphologic changes, quantitated by computer-assisted morphometry of neurite length and number per soma, and metabolic changes, indicated by alterations in ornithine decarboxylase activity (ODC). In addition, the interaction of each ganglioside with nerve growth factor (NGF) was investigated with an NGF-responsive pheochromocytoma PC12 cell line and NGF-insensitive neuroblastoma Neuro-2a cultures. PC12 cells responded to gangliosides only in the presence of NGF (20 micrograms/ml): GM1 produced the greatest morphologic response, but did not alter metabolic levels; GT1b increased both parameters. The presence (5 micrograms/ml) or absence of NGF did not have an effect on the ganglioside-mediated morphologic responses of Neuro-2a cells to each species: GD1b elicited the greatest increase in neurite length, while GD1a and GT1b stimulated both length and number. In contrast, while GT1b alone was able to elevate ODC activity independently of NGF, the simultaneous exposure of Neuro-2a cultures to NGF and GM1 or GD1a resulted in a stimulation of cellular metabolism. These results indicate that each ganglioside species has a specific target action in the stimulation of different trophic responses and that performance in one category is not a predictor of the result in another. In addition, it is possible to confer a sensitivity to NGF by simultaneous treatment with specific gangliosides. This indicates that membrane gangliosides may modulate the actions of neurotrophic factors.
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PMID:Neuritogenic and metabolic effects of individual gangliosides and their interaction with nerve growth factor in cultures of neuroblastoma and pheochromocytoma. 370 79

A mouse neuroblastoma cell line (clone NS20Y) is highly tumorigenic in syngeneic A/J mice. When this clone was persistently infected with measles virus (NS20Y/MS) it failed to grow or form tumors in conventional A/J or nude mice, even when large numbers of cells were inoculated. As doubling time, serum dependence, and anchorage-independent growth on agar did not differ significantly between NS20Y and NS20Y/MS, lack of tumorigenicity of the persistently infected cells is unlikely to be due to an intrinsic property of the cells. NS20Y/MS cells were found to be effectively rejected in athymic nude as well as conventional syngeneic mice. However, injection of mice with either anti-interferon or anti-asialo GM1 serum, both of which have been shown to deplete natural killer (NK) cells in vivo, enabled NS20Y/MS cells to form large tumors. Unexpectedly, treatment of mice with silica also allowed the NS20Y/MS cells to form tumors. Under these conditions, it was shown that silica caused a significant decrease in NK activity as late as 7 days after a single injection. Although NS20Y/MS were not susceptible to NK cell lysis in vitro, the in vivo data suggest that NK cells are in fact the prime mechanism in the rejection of this persistently virus-infected neuroblastoma cell line by athymic and conventional syngeneic mice. The results indicate that NK activity may be greater or more sensitively detected in vivo than in vitro.
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PMID:Persistent viral infection affects tumorigenicity of a neuroblastoma cell line. 387 58

Previous reports from our laboratory showed that tetrasialoganglioside GQ1b, when exogenously added, can promote cell proliferation and neurite outgrowth in two human neuroblastoma cell lines, GOTO and NB-1 (Tsuji, S., Arita, M. and Nagai, Y. (1983) J. Biochem. 94, 303-306). To clarify the activity-associated structure of GQ1b, we analyzed the structure-activity relationships using the GQ1b molecule, derivatives of it, and related gangliosides. When the GQ1b molecule was divided into two parts, the ceramide and oligosaccharide moieties, no activity was found with the former, while with the latter the activity could be seen, although the level of activity obtained never exceeded half that of GQ1b itself and an optimal concentration of 100-200 ng/ml of 20-40-times that of native GQ1b (5 ng/ml) was required. Furthermore, the activity of GQ1b was completely abolished by neuraminidase treatment, which converted GQ1b to GM1, so we examined other molecular species of gangliosides having a common gangliotetraose backbone but linked differently with two to four sialic acids (i.e., GD1a, GD1b, GT1a, GT1b, GQ1b and GQ1c). Among them, only GQ1b was found to be active. The results disclosed the interesting fact that deletion of any sialic acid residue from either of the two disialosyl residues of GQ1b results in a complete loss of activity and that the mere existence of the tetrasialosyl structure does not lead to activity; this indicates the absolute necessity of the GQ1b oligosaccharide structure for the expression of activity. For full expression of the activity, both the ceramide and oligosaccharide moieties were necessary. It was also found that the GQ1b oligosaccharide inhibited the activity of GQ1b at a concentration a few times greater than that of GQ1b, suggesting the involvement of a receptor-like mechanism in the action of GQ1b at the cell membrane.
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PMID:Bioactive gangliosides: analysis of functional structures of the tetrasialoganglioside GQ1b which promotes neurite outgrowth. 394 70

To compare the subcellular distribution of endogenously synthesized and exogenous gangliosides, cultured murine neuroblastoma cells (N1E-115) were incubated in suspension for 22 h in the presence of D-[1-3H]galactose or [3H]GM1 ganglioside, transferred to culture medium containing no radioisotope for periods of up to 72 hr, and then subjected to subcellular fractionation and analysis of lipid-sialic acid and radiolabeled ganglioside levels. The results indicated that GM2 and GM3 were the principal gangliosides in the cells with only traces of GM1 and small amounts of disialogangliosides present. About 50% of the endogenously synthesized radiolabelled ganglioside in the four major subcellular membrane fractions studied was recovered from plasma membrane and only 10-15% from the crude mitochondrial membrane fraction. In contrast, 45% of the exogenous [3H]GM1 taken up into the same subcellular membrane fractions was recovered from the crude mitochondrial fraction; less than 15% was localized in the plasma membrane fraction. The results are similar to those obtained from previously reported studies on membrane phospholipid turnover. They suggest that exogenous GM1 ganglioside, like exogenous phosphatidylcholine, does not intermix freely with any quantitatively major pool of endogenous membrane lipid.
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PMID:Studies on the turnover and subcellular localization of membrane gangliosides in cultured neuroblastoma cells. 400 Mar 96

Individual ganglioside species (possessing the gangliotetrose oligosaccharide) were purified from bovine brain gray matter and applied in varying concentrations to the culture medium of mouse neuroblastoma cells (N2A) in vitro. After 48 hr of incubation, the cells were stained, and the neuritogenic response quantitated with a video analysis system, employing a program to measure three parameters of neuroblastoma differentiation: neurites per cell (sprouting), neurite length (extension), and degree of neurite branching (arborization). All the individual gangliosides tested promoted neurite extension in a dose-dependent fashion. Asialogangliosides ("neutral" glycosphingolipids) were without effect, which suggests that sialic acid (N-acetylneuraminic acid) is necessary to elicit this cellular response. With increasing concentrations of GM1 (5 to 500 micrograms/ml), the average cellular neurite length increased significantly, whereas the number of neurites per cell decreased. With the trisialoganglioside GT1b, neurite length did not increase to the extent seen with GM1, but an increase in the number of neurites per cell (sprouting) and branch points per neurite (arborization) was observed. These results suggest that the in vitro neuronal response to exogenous gangliosides may combine specific responses to individual species making up the total.
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PMID:Quantitation of the in vitro neuroblastoma response to exogenous, purified gangliosides. 400 44

A ganglioside-stimulated protein phosphorylation system was discovered in plasma membrane fractions of human neuroblastoma cells (GOTO). Gangliosides (GQ1b, GT1a, GT1b, GD1a, GD1b, GD3, and GM1) could stimulate this system. GQ1b showed the most effective stimulation among these gangliosides. The substrate specificity was rather broad. Not only some (de novo) proteins of the membranes but also purified histones and tubulin were phosphate-acceptable. This protein phosphorylation system specifically depended upon Ca2+ (optimum concentration: 50-100 microM). The optimum pH was 7.0-7.5. GQ1b/Ca2+ could not directly activate well known protein kinases (Ca2+/phospholipid-activated protein kinase, Ca2+/calmodulin-activated protein kinase, and cyclic nucleotide-dependent protein kinases). Furthermore, GQ1b could replace neither phospholipids nor calmodulin. Thus, an unknown, new type of protein kinase(s) may be involved in this system. Alternatively, GQ1b may activate some known protein kinase(s) in cooperation with another unknown factor which may be removed during the preparation of the partially purified known protein kinase used in this experiment.
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PMID:Bioactive gangliosides. IV. Ganglioside GQ1b/Ca2+ dependent protein kinase activity exists in the plasma membrane fraction of neuroblastoma cell line, GOTO. 401 42

Incubations in vitro of GA1, labeled with 3H in the terminal D-galactopyranosyl group, with nonradioactive CMP-NeuNAc in the presence of homogenates of C21 rat brain glial cells, NIE mouse neuroblastoma cells, 3T3 mouse fibroblasts, SV 40-transformed 3T3 cells, chick embryo fibroblasts, Rous sarcoma virus-transformed chick embryo fibroblasts, and 9-day old rat brain resulted in all cases in the formation in high yield of GM1b, in which the neuraminidase-labile NeuNAc group is linked at O-3 of the terminal D-galactosyl residue, as shown by permethylation studies. No trace of the naturally occurring neuraminidase-stable GM1a was detected in any case. In addition, with NIE cells, and normal and RSV-transformed chick embryo fibroblasts, a disialosylganglioside (GD1) differing from GD1a and GD1b, and bearing only one substituent at O-3 of the terminal D-galactopyranosyl residue was formed. It was also biosynthesized from GM1b and CMP-NeuNAc by NIE and chick embryo cells but not by C21 cells, or rat brain. However, C21 cells and rat brain were capable of synthesizing GD1a from GM1a. Periodate oxidation degraded both NeuNAc groups in GD1 to a 7-carbon fragm:nt, indicating lack of substitution at O-8. GM1b could not be detected as a natural product in rat brain.
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PMID:Biosynthesis in vitro of mono- and di-sialosylgangliosides from gangliotetraosylceramide by cultured cell lines and young rat brain. Structure of the products, and activity and specificity of sialosyltransferase. 624 13


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