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 specific interaction of the cytolytic Clostridium perfringens delta toxin with membrane GM2 was indicated by: (i) characterization of this glycolipid in the membrane of sheep and goat erythrocytes, which are lysed by the toxin, whereas GM2 was undetectable in insensitive rabbit erythrocytes, (ii) demonstration of 125I-toxin binding to GM2, by autoradiography, following incubation with thin-layer chromatograms containing separated neuroblastoma gangliosides, and (iii) toxin fixation by phospholipid-cholesterol unilamellar vesicles containing either sheep gangliosides or GM2. In order to investigate the intramembrane events leading to membrane disruption following toxin binding, the photoreactive probe 12(4-azido-2-nitrophenoxy)stearoyl 1-14C glucosamine, which inserts into the outer layer and labels integral membrane proteins, was used to establish whether delta toxin penetrates into target cell membrane. No toxin labeling was found, suggesting that toxin action takes place at the membrane surface. This contention is supported by the observation that despite toxin binding, GM2 liposomes did not release entrapped 14C-glucose. Treatment of toxin with carboxypeptidases, but not aminopeptidases, abolished both toxin binding capacity onto erythrocytes and its combination with antitoxin neutralizing antibodies, suggesting that the carboxy terminal end of the toxin is critical for binding to cell membrane.
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PMID:Interaction of Clostridium perfringens delta toxin with erythrocyte and liposome membranes and relation with the specific binding to the ganglioside GM2. 255 36

Seven monoclonal antibodies (mAbs) reactive with ganglioside II3(NeuAc)2-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, DMAb-8, and DMAb-17) with melanoma line SK-MEL 28, which contains 1.4 nmol sialic acid of GD3 per mg protein. The specificities of the mAbs were defined by high-performance thin-layer chromatography (HPTLC) immunostain and solid-phase radioimmunoassay (SP-RIA) with a panel of purified gangliosides. DMAb-7 and DMAb-8 reacted with GD3, IV3(NeuAc)2nLcOse4Cer(3',8'-LD1), and very weakly with IV3(NeuAc)2II3NeuAcGgOse4Cer (GT1a), but not with II3NeuAc-LacCer (GM3), II3NeuAcGgOse3Cer(GM2), II3NeuAcGgOse4Cer (GM1), II3NeuAc, IV3NeuAcGgOse4Cer (GD1a), II3(NeuAc)2GgOse3(GD2), II3(NeuAc)2GgOse4Cer (GD1b), IV3NeuAcII3(NeuAc)2, GgOse4Cer(GT1b), suggesting the binding epitope to be a terminal tetrasaccharide NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4(Glc or GlcNAc). DMAb-7 and DMAb-8 were used to investigate the expression of GD3 on cultured human tumor cells of neuroectodermal origin. Thirteen of 19 gliomas, 3 of 5 medulloblastomas, 5 of 5 neuroblastomas, 2 of 2 melanomas, and 1 of 3 teratomas were shown to react with DMAb-8 and/or DMAb-7 by cell surface-RIA (CS-RIA) and immunofluorescence (IF) assays. HPTLC and densitometric analysis confirmed these results, as positive immunostains in the GD3 region were obtained with oligoganglioside fractions from 9 glioma, 1 medulloblastoma, 2 neuroblastoma, 1 melanoma, and 1 teratoma cell line. Glioma cell line U-105 MG and medulloblastoma cell line Daoy contain GD3 as shown by HPTLC immunostain analysis of extracts, although GD3 was undetectable on the cell surface as determined by CS-RIA and IF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GD3 expression by cultured human tumor cells of neuroectodermal origin. 260 39

Abnormalities of ganglioside structure characterize the neoplastic state, and aberrant glycosylation has been implicated as underlying many new tumor ganglioside structures. However, variations in ceramide structure can also result in novel tumor gangliosides. To address systematically this aspect of ganglioside metabolism, we have initiated a study of the structures of the ceramide species of an oligosaccharide-homogeneous human tumor-derived ganglioside, GM2. The ganglioside was isolated from neuroblastoma tissue and purified by normal-phase high pressure liquid chromatography. Marked ceramide heterogeneity was observed; 18 individual ceramide species of neuroblastoma GM2 were separated by reversed-phase high pressure liquid chromatography and collected. Their structures were determined by a combination of negative- and positive-ion fast atom bombardment mass spectrometry and collisionally activated dissociation tandem mass spectrometry of the underivatized gangliosides. The striking finding was the detection of alpha-hydroxylation of a significant fraction of each of the major fatty acid species (16:0, 18:0, 20:0, 22:0, and 24:1); alpha-hydroxylated species quantitatively represented almost one-fifth of the total tumor GM2 species. Fatty acyl hydroxylation was also detected in the ceramide of several other human tumor gangliosides. In contrast, as previously known, fatty acyl hydroxylation was not detected in the normal human brain gangliosides GM3, GM2, and GM1. We propose that aberrant fatty acid alpha-hydroxylation is a novel and sometimes quantitatively significant characteristic of human tumor ganglioside metabolism.
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PMID:Aberrant fatty acyl alpha-hydroxylation in human neuroblastoma tumor gangliosides. 274 31

Concentration of gangliotriaose-series glycosphingolipids, including GA2, GM2, GD2 and GT2, was measured in human sera by a thin-layer chromatography/enzyme-immunostaining method. By this method, as little as 5-10 ng/ml of these glycolipids in serum could be determined simultaneously. Although GD2 ganglioside could be consistently detected in normal cord blood (1-2 ng/ml of serum), the ganglioside was never detected in normal adult serum. However, the same ganglioside was found to be present in large quantity in preoperative sera of 6/9 patients with neuroblastomas (25-658 ng/ml of serum). In addition to GD2, gangliosides GM2 and GA2 increased concomitantly than usual. It is concluded that this highly sensitive quantification of the tumor-associated glycolipids circulating in serum of neuroblastoma patients could be useful in their diagnosis.
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PMID:Detection of gangliotriaose-series glycosphingolipids in serum of cord blood and patients with neuroblastoma by a sensitive TLC/enzyme-immunostaining method. 330 Jul 82

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

As suggested by Hakomori, one of the mechanisms to explain the abnormal proliferation of tumor cells by loss of contact inhibition could be a modification of membrane gangliosides. We report here a case of neuroblastoma with opsomyoclonia in which the ganglioside profile is abnormal, with a high level of GP3 and GM2, and of other gangliosides which are not present in normal child and adult brains.
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PMID:[Interest of ganglioside analysis in the neuroblastoma (author's transl)]. 625 46

Exposure of mouse neuroblastoma cell line N4TGl to opiates or [D-Ala2,D-Leu5] enkephalin produced a naloxone-reversible inhibition of cyclic AMP synthesis and prevented, in a concentration-dependent manner, the formation of both ganglioside GM2 (GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM3 (NeuNAc-Gal-Glc-ceramide) and ganglioside GM1 (Gal-GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM2 in cell-free extracts. In contrast, the receptor-mediated elevation of intracellular cyclic AMP levels by agents such as prostaglandin E1 (in the presence of isobutylmethylxanthine) or the addition of the cyclic AMP derivatives (dibutyryl cyclic AMP) markedly stimulated the activities of UDP-GalNAc:GM3,N-acetylgalactosaminyltransferase and UDP-Gal:GM2,galactosyltransferase. An overall increase in the synthesis of gangliosides more complex than GM3 was also observed in the mouse neuroblastoma x hamster brain explant hybrid cell line NCB-20 following elevation of cyclic AMP levels by treatment with serotonin and pargyline. The data presented support the hypothesis that cyclic AMP may have a role in the regulation of sialoglycosphingolipid biosynthesis.
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PMID:Possible role of cyclic AMP in the receptor-mediated regulation of glycosyltransferase activities in neurotumor cell lines. 626 98

Cellular differentiation of the neuroblastoma X glioma hybrid cell line NG108-15 was measured and correlated with quantitative changes in the cells' ganglioside composition. The degree of differentiation was measured using an enzymatic marker, choline acetyltransferase (CAT), which is responsible for neurotransmitter synthesis in this cell line. Differentiation of these cells is commonly induced by agents such as dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). However, in our studies, we observed that these cells "self-differentiated," in the absence of chemical inducers, when the cells became dense in culture. The differentiation marker, CAT specific activity, rose from 150 to more than 400 pmol/min/mg of protein as cell density increased, attaining a level higher than that achieved by treatment with Bt2cAMP. Differentiation of sparse cultures could be induced by conditioned medium removed from dense cultures. This effect was not due to depletion of a serum component from the medium by the cells, since it was not mimicked by serum depletion or inhibited by addition of fresh serum to the conditioned medium. These data suggest that cell density-dependent differentiation was caused by release of a factor from the cells which induced differentiation in a concentration-dependent manner. Gangliosides, therefore, were purified from sparse control cultures, dense cultures, and cultures treated with the differentiating agents Bt2cAMP, prostaglandin E1 (plus theophylline), or butyric acid. Quantitative thin layer chromatography revealed that all of the cultures contained the four gangliosides GM3, GM2, GM1, and GD1a. The concentration of one of the gangliosides, GM2, increased markedly (up to 12-fold) during differentiation. The GM2 concentration correlated closely with the level of CAT activity in the different cultures (r = 0.99). These data demonstrate that the ganglioside concentration in these cells is regulated during differentiation, a finding consistent with a possible role for gangliosides in the differentiated phenotype.
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PMID:Ganglioside composition is regulated during differentiation in the neuroblastoma X glioma hybrid cell line NG108-15. 630 Mar 57

The effect of methylmercuric chloride (CH3HgCl) on the levels of gangliosides in mouse neuroblastoma cells (NBP2) in culture was studied. The treatment of NB cells with low concentrations (0.1 microM and 0.2 microM) of CH3HgCl, which did not affect the growth rate or morphology, caused an increase in the level of the GM3 ganglioside without changing the level of other gangliosides. The treatment of NB cells with higher concentrations (0.5 microM and 1 microM) of CH3HgCl, which inhibited the growth of NB cells, caused a decrease in the level of GM3 and an increase in the level of GM2. These results show that alterations in the levels of specific gangliosides can be observed in cells which do not exhibit any detectable change in growth rate or morphology. This change may be associated with subtle changes in brain functions, including behavioral and psychological changes, after exposure to low concentrations of organic mercury.
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PMID:Effect of methylmercuric chloride on gangliosides of mouse neuroblastoma cells in culture. 663 74

The influence of divalent cations on glycosphingolipid metabolism was examined in the NB41A mouse neuroblastoma clonal cell line. HPLC methods were utilized to quantitate the effects on neutral glycolipids and monosialogangliosides. NB41A cells were shown to contain GM3, GM2, GM1, GD3, and GD1a by HPLC and TLC. The neutral glycosphingolipids consisted of glucosylceramide (GlcCer), lactosylceramide (LacCer), GalNAc (beta 1 leads to 4) Gal(beta 1 leads to 4)Glc(beta 1 leads to 1)Cer (GgOse3Cer), and GalNAc(beta 1 leads to 3)Gal(alpha 1 leads to 4) Gal(beta 1 leads to 4)Glc(beta 1 leads to 1)Cer (GbOse4Cer) according to their HPLC behavior. Cells grown in the presence of 1.85 mM-EGTA showed a two-to threefold increase in GM3 whereas other glycosphingolipids were only slightly affected. When cells were grown in the presence of 1.45 mM-EGTA plus 0.4 mM-EDTA a similar increase in GM3 was observed but this change was now accompanied by decreases in GM2, GM1, GgOse3Cer. The EGTA-EDTA effects were reversed when growth was in the presence of Ca2+ sufficient to bind all chelator. Mn2+ replacement reversed the chelator effects differentially; GM2 and GM1 levels were the most sensitive to increases in Mn2+ concentration; GgOse3Cer and GbOse4Cer were also sensitive, whereas GM3 was the least affected. These results suggest calcium serves an important regulatory role on GM3 levels and that manganese concentration may regulate the levels of galactosamine-containing glycolipids in mouse NB41A neuroblastoma cells.
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PMID:Effects of divalent cations on the glycolipids from cultured mouse neuroblastoma cells. 680 99


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