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)

Two different glycolipid:fucosyltransferase activities involved in the biosynthesis in vitro of blood group-related glycosphingolipids have been detected in a membrane preparation isolated from a human neuroblastoma-derived clonal cell line, IMR-32. The membrane preparation contains an alpha (1,2)-fucosyltransferase (EC 2.4.1.89) that catalyzed the transfer of vucose from GDP--[14C]fucose to neolactotetraosylceramide or neolactopentaosylceramide to form types H-I and B-I glycolipids, respectively. The second fucosyltransferase catalyzes the transfer of fucose to lactotriaosylceramide [GlcNAc(beta1-3)Gal(beta1-4)Glc-Cer] to form a tetraglycosylceramide intermediate of the novel Lea-type glycolipid. UDP-galactose:lactotriaosylceramide beta-galactosyltransferase (EC 2.4.1.86) had 4 times the activity of UDP-galactose:alpha-galactosyltransferase (EC 2.4.1.87) when tested under similar conditions. alpha-Fucosyltransferase activities and the incorporation of [14C]fucose into glycoproteins and glycolipids were also compared in cells differentiated in the presence of 4 micron BrdUrd and 6-mercaptoguanosine.
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PMID:Biosynthesis in vitro of fucose-containing glycosphingolipids in human neuroblastoma IMR-32 cells. 27 43

Conjugates of horseradish peroxidase with the lectins ricin (d-galactose), wheat germ agglutinin (N-acetylglucosamine), phytohemagglutinin (N-acetylgalactosamine), and with cholera toxin (GM1 ganglioside) were used for a cytochemical detection of corresponding termin al carbohydrates, or glycolipids on cell surfaces of cultured neurons and neuroblastoma cells. Cells were labeled at 4 degrees C with the above ligands and their adsorptive endocytosis was studied after incubations at 37 degrees C in a medium free of ligand. Peroxidase was detected by the method of Graham and Karnovsky (J. Histochem. Cytochem. 14:291, 1966). Lectins and cholera toxin underwent endocytosis in cisternae and vesicles of GERL (Golgi-Endoplasmic Reticulum-Lysosome). We suggest that GERL is the primary ercipieint of adsorptively endocytosed plasma membrane "receptor"-ligand complexes which are thus degraded or possibly reutilized (recycling). Wheat germ agglutinin-horseradish peroxidase conjugates used in vivo for studies of retrograde axonal transport were significantly more sensitive than free horseradish peroxidase.
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PMID:The use of lectins and cholera toxin for the detection of surface carbohydrates of cultured neurons and neuroblastoma. 47 60

Two ganglioside-associated protein components I and II have been isolated from crude ganglioside preparations of calf brain by DEAE-Sephadex ion-exchange chromatography. Both components exhibited binding capacity in aqueous media for gangliosides of the 'ganglio' series but not for neutral glycosphingolipids (polyglycosylceramides) and only a low capacity for sialosylparagloboside. Each protein bound individual gangliosides with different efficiency. Upon prolonged incubation of component I with gangliosides, complexes with high (30:1) and low (6:1) glycolipid/protein molar ratios were formed. The latter but not the former complex was able to penetrate Sephadex G-200 beads. Both components inhibited plating efficiency of cultured mouse N2a neuroblastoma cells. The molecular masses of components I and II were determined by SDS/PAGE to be 11-12 kDa and 28 kDa, respectively. Carbohydrates (fucose, mannose, galactose, N-acetylglucosamine, N-acetylgalactosamine, and some sialic acid) were found only in component II. When examined by reverse-phase HPLC each component separated into two major closely migrating peaks which were subsequently examined by Edman degradation. Amino acid sequences of the N-terminal portions of three of these peaks (one peak from component I and both peaks from component II) showed, as far as the sequences were established, identity with the sequence of ubiquitin. It is hypothesized that the proteins may be instrumental in intracellular trafficking of gangliosides.
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PMID:Ganglioside binding proteins of calf brain with ubiquitin-like N-terminals. 133 54

Fucosyl residues in the alpha 1----3 linkage to N-acetylglucosamine (Fuc alpha 1----3GlcNAc) on oligosaccharides of glycoproteins and glycolipids have been detected in certain human tumors and are developmentally expressed (reviewed in Foster, C. S., and Glick, M. C. (1988) Adv. Neuroblastoma Res. 2, 421-432). In order to understand control mechanisms for the biosynthesis of these fucosylated glycoconjugates, GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1----3fucosyltransferase was purified from human neuroblastoma cells, CHP 134, utilizing either the immobilized oligosaccharide or disaccharide substrates. The enzyme, extracted from CHP 134 cells, was purified by DEAE- and SP-Sephadex chromatography and then by either immobilized substrate. alpha 1----3Fucosyltransferase was obtained in approximately 10% yield and was purified 45,000-fold from the cell extract. The kinetic properties of the enzyme showed an apparent KGDP-Fuc 43 microM, KGal beta 1----4GlcNAc 0.4 mM, KGal beta 1----4Glc 8.1 mM, and KFuc alpha 1----2Gal beta 1----4Glc 1.0 mM. Polyacrylamide gel electrophoresis of the affinity-purified enzyme showed two proteins which migrated, Mr = 45,000-40,000. The enzyme differed in substrate specificity, pH optimum, response to N-ethylmaleimide and ion requirements from the enzymes purified from human milk or serum. The inability of alpha 1----3fucosyltransferase to transfer to substrates containing NeuAc alpha 2----3 or alpha 2----6Gal is in contrast to the reports for the enzyme in other human tumors. This substrate specificity correlates with the oligosaccharide residues thus far defined on glycoproteins of CHP 134 cells since NeuAc and Fuc alpha 1----3GlcNAc have yet to be detected on the same oligosaccharide antenna. However, the enzyme transfers to Fuc alpha 1----2Gal beta 1----4GlcNAc/Glc with higher activity than the unfucosylated disaccharides, although neither alpha 1----2fucosyltransferase nor Fuc alpha 1----2 residues have been detected in CHP 134 cells. The different substrate specificities of alpha 1----3fucosyltransferase isolated from human tumors and normal sources leads to the suggestion that a family of alpha 1----3fucosyltransferases may exist and that they may be differentially expressed in human tumors.
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PMID:Purification and characterization of GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1----3fucosyltransferase from human neuroblastoma cells. Unusual substrate specificities of the tumor enzyme. 199 16

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

'Suicide transport' is a term coined to describe the use of retrogradely axonally transported toxin to produce anatomically selective neural lesions. As a first step in developing neuron type-selective, systemically non-toxic suicide transport agents, a prototype hybrid toxin consisting of ricin A-chain (RTA) disulfide coupled to wheat germ agglutinin (WGA) was synthesized by first derivatizing WGA by reaction with N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP) in the presence of N-acetylglucosamine and then formation of WGA-SS-RTA by mixing the derivatized WGA with reduced RTA. The ability of this conjugate to inhibit protein synthesis was tested on two cell lines in vitro; the ID50 was 0.2 nM using the K562 hematopoietic stem cell line and 0.02 nM for the 2a neuroblastoma cell line. Suicide transport activity was assessed by microinjection of hybrid into the cervical vagus nerve of rats. Intact WGA-SS-RTA, but not hybrid that was pretreated with dithiothreitol to uncouple RTA from the WGA carrier, reliably killed vagal motor neurons. Both intact and reduced hybrid killed vagal sensory neurons. Indirect peroxidase immunohistochemistry demonstrated transport of RTA to vagal sensory neurons and WGA to both vagal sensory and motor neurons. These results are the first evidence that a hybrid toxin can be active as a suicide transport agent.
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PMID:Wheat germ agglutinin-ricin A-chain conjugate is neuronotoxic after vagal injection. 301 47

N-Acetylneuraminic acid (Neu5Ac) and [6-2H]-Neu5Ac were prepared from 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine). Then Henry reaction of a 1-deoxy-1-nitro derivative of GlcNAc (protected 1-C-nitroanhydro-D-glucitol) with cyclohexylidene-D-glyceraldehyde, followed by successive acetylation and reductive denitration with Bu3SnH, gave an anhydrononitol intermediate (6) diastereo-selectively in high yields. Debenzylidenation of 6 freed its distal primary carbinol group, which was subjected to catalytic oxidation followed by hydrolysis, esterification (diazomethane), and acetylation to give a protected methyl nononate. This ester was transformed into the known methyl N-acetyl-4,7,8,9-tetra-O-acetyl-2,3-dehydroneuraminate (15), which was identical with a sample prepared from Neu5Ac. Neu5Ac was obtained from 15 by bromoetherification (NBS, methanol) followed by reductive debromination with Bu3SnH and hydrolysis. Similarly, the [6-2H]-derivative of 15 was transformed into [6-2H]-Neu5Ac.
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PMID:A synthesis of N-acetylneuraminic acid and [6-2H]-N-acetylneuraminic acid from N-acetyl-D-glucosamine. 362 Dec 40

The presence of fucosyl residues linked alpha 1----3(4) to N-acetylglucosamine was demonstrated on the oligosaccharides from glycoproteins of 11 human neuroblastoma tumors from ten different patients. This finding is in complete agreement with the previous report that human neuroblastoma cell lines contained an unusually large proportion of metabolically incorporated L-[3H]fucose in this specific linkage (U. V. Santer and M. C. Glick, Cancer Res., 43:4159-4166, 1983). Furthermore, the glycopeptides derived from the neuroblastoma tumors had a low percentage of fucose-containing biantennary oligosaccharides as determined by affinity to concanavalin A-Sepharose and in this characteristic were similar to glycopeptides from virus transformed and other tumor cells. To obtain these results, the tumor cells were labeled metabolically for 48 h with L-[3H]fucose. The cells were harvested and digested with Pronase, and the glycopeptides were isolated and treated with alpha-L-fucosidase from almonds, specific for the release of fucose linked alpha 1----3(4) to N-acetylglucosamine. A portion of the glycopeptides was characterized by serial affinity chromatography on immobilized concanavalin A and lentil lectin. The phenotypic similarity of the tumor cells to the cell lines, particularly CHP-134, included the paucity of biantennary oligosaccharides and the presence of fucosyl residues on the multiantennae of the glycopeptides.
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PMID:Similarities in glycosylation of human neuroblastoma tumors and cell lines. 370 96

Biosynthetically radiolabelled heparan sulphate proteoglycans have been isolated from the growth medium and the cell lysate of a human neuroblastoma cell line (CHP100). Chromatography on Sepharose CL-4B identified two heparan sulphate proteoglycans in the medium (Kav 0.220 and 0.389), whereas in the cell lysate the major proteoglycan species were more heterogenous and of a smaller overall molecular size (Kav 0.407) than the medium-derived counterparts. Chromatography on Sepharose CL-6B of free heparan sulphate glycosaminoglycan chains showed that the majority of cell-layer-derived material heparan sulphate 2, Kav = 0.509) was smaller than medium heparan sulphates (heparan sulphate 1 and heparan sulphate 2, Kav 0.230 and 0.317). Analysis of the patterns of polymer sulphation by nitrous acid treatment, gel chromatography and high-voltage electrophoresis established that in each heparan sulphate fraction there was on average 1.1 sulphate residues per disaccharide with an N:O sulphate ratio of 1.1. Heparan sulphate in the medium had a high proportion of di-O-sulphated disaccharides in regions of the chain with repeat disaccharide sequences of structure GlcA-GlcNSO3, whereas cell-associated material was enriched in di-O-sulphated tetrasaccharides of alternating sequences GlcA-GlcNAc-GlcA-GlcNSO3. The identification of several populations of heparan sulphate proteoglycans differing in molecular size and glycosaminoglycan fine structure may reflect the functional diversity of this family of macromolecules in the nervous system.
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PMID:Heterogeneity of cell-associated and secretory heparan sulphate proteoglycans produced by cultured human neuroblastoma cells. 623 54

The antibiotic tunicamycin blocks the transfer of GlcNAc-1-P from UDP-GlcNAc to dolichol phosphate, thereby blocking the synthesis of N-linked oligosaccharide chains on glycoproteins. Its effect on the biosynthesis of gangliosides has not been reported. We report that tunicamycin caused a 70-80% reduction in incorporation of [(3)H]GlcN into gangliosides and neutral glycosphingolipids of the neuroblastoma-glioma hybrid cell line NG 108-15 at antibiotic concentrations that caused a 90% reduction of the radiolabel incorporation into glycoproteins. The effect of tunicamycin on ganglioside biosynthesis was apparent after only 4 hr of incubation, and maximum inhibition was seen within 6 hr. When control or tunicamycin-treated (5 mug/ml) cells were collected and fractionated to separate glycoproteins, neutral glycosphingolipids, gangliosides, and nucleotide sugar-precursor pools, the following results were obtained: (i) UDP-GlcNAc and UDP-GalNAc pool sizes increased >3-fold, and specific activities decreased 50% upon treatment with tunicamycin; (ii) when corrected for this value, the percentage inhibition of GlcN incorporation into various glycoconjugates by tunicamycin in these cells was 82% for glycoproteins, 54% for neutral glycosphingolipids, and 50% for gangliosides; and (iii) the different gangliosides were affected differentially, with the most striking inhibition apparent in GM(3) biosynthesis, which was decreased 78% in the presence of tunicamycin. These data suggest that the effects of tunicamycin on glycosphingolipids as well as on glycoproteins must be considered when interpreting its effects on intact cells and organisms.
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PMID:Tunicamycin inhibits ganglioside biosynthesis in neuronal cells. 657 17


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