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At least 127 records · Page 7Linked to original sources
PubMed1985

Effects of lesions and ganglioside GM1 treatment on striatal polyamine levels and nigral DA neurons. A role of putrescine in the neurotropic activity of gangliosides.

The effects of a partial hemitransection at the meso-diencephalic level, with or without chronic ganglioside GMI treatment, have been evaluated on striatal polyamine levels, 7, 14 and 21 days after lesion, as well as on the ability of the polyamine synthesis inhibitor alpha-difluoromethylornithine (alpha-DFMO) to modulate the protective effects of chronic ganglioside GMI treatment against retrograde degeneration of the nigral dopamine (DA) nerve cell bodies (14 day time interval). The striatal polyamine levels were measured by high pressure liquid chromatography after dansylation of the polyamines. The nigral DA nerve cells were studied by means of tyrosine hydroxylase (TH) immunocytochemistry using the indirect immunoperoxidase technique. Quantitation was performed by means of morphometrical evaluation of the TH immunoreactive area of the substantia nigra. Seven days after partial hemitransection there is a marked increase (above 350%) in striatal putrescine levels, which is not modulated by chronic GMI treatment. This marked increase could, to a large extent, be counteracted by simultaneous treatment with alpha-DFMO, which blocks mainly the synthesis of putrescine. Twenty-one days after lesion chronic GMI treatment could produce an increase in striatal putrescine levels on the intact side and also after this time-interval prevent the reduction of striatal spermine levels. It was also found that simultaneous treatment with alpha-DFMO prevents the development of the protective action of chronic ganglioside GMI treatment against retrograde degeneration of the nigral DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Sequential immunization of melanoma patients with GD3 ganglioside vaccine and anti-idiotypic monoclonal antibody that mimics GD3 ganglioside.

GD3 ganglioside is an attractive target for immunotherapy of melanoma because it is abundantly expressed on all melanomas but not expressed on most normal tissues. Although GD3 has proven to be one of the least immunogenic gangliosides, our recent studies showed that anti-GD3 antibodies can be induced in patients immunized either with GD3-lactone-KLH (GD3-L-KLH) plus QS-21 adjuvant or with BEC2 anti-idiotypic monoclonal antibody vaccine, which mimics GD3, plus Bacillus Calmette-Guérin. We compared the immunogenicity of these two vaccines and tested whether one vaccine could prime an antibody response to the other. This is the first clinical trial immunizing patients with both antigen and anti-idiotypic monoclonal antibody vaccine. Twenty-four melanoma patients were randomized to be immunized with either BEC2 followed by GD3-L-KLH or in the opposite order. Our prior study suggested that a 25-microg dose of BEC2 was more immunogenic than our standard dose of 2.5 mg and therefore was used in this trial. Overall, 10 of 24 patients (42%) developed anti-GD3 antibodies detectable by ELISA, five in each cohort. All antibody responses were in response to the GD3-L-KLH vaccine. We found no evidence of priming by either vaccine. Antibody responses did not correlate with survival outcomes. Cellular responses were detected by enzyme-linked immunospot against BEC2, Bacillus Calmette-Guérin, and KLH, but not against GD3. We confirmed that GD3-L-KLH vaccine induces anti-GD3 antibodies, but we were unable to confirm our previous finding that a 25-microg dose of BEC2 is immunogenic. Future multivalent ganglioside vaccines should include the GD3-L-KLH vaccine.

Adolescent↗
PubMed1980

Action of ortho- and paramyxovirus neuraminidase on gangliosides. Hydrolysis of ganglioside GM1 by Sendai virus neuraminidase.

The action of neuraminidase of influenza A virus, Sendai virus and Newcastle disease virus particles on bovine brain ganglioside GM1 and the properties of Sendai virus neuraminidase for GM1 were studied. With Sendai virus, GM1 was hydrolyzed to asialo-GM1 (GA1) and N-acetylneuraminic acid even in the absence of surfactant or other additives, while the hydrolysis of GM1 by Newcastle disease virus or influenza A virus was very low or undetectable under the same conditions. The formation of GA1 by Sendai virus neuraminidase was confirmed by thin-layer chromatography and immunodiffusion test using anti-GA1 antiserum. The apparent Km of Sendai virus neuraminidase for GM1 hydrolysis was found to be 2.67 x 10(-4) M and the optimum pH was 5.6. GM3, GM2 and oligosaccharide of GM1 were hydrolyzed more effectively than GM1 in the absence of surfactant (GM3 greater than GM2 greater than oligosaccharide of GM1 greater than GM1). The hydrolysis of GM1 by the Sendai virus enzyme was stimulated by the addition of sodium cholate or sodium taurocholate, but was inhibited by divalent cations (10 mM), Ca2+, Mg2+, ZN2+, Fe2+ and CU2+. In the absence of the surfactant, Sendai virus neuraminidase hydrolyzed GM1 more efficiently than Arthobacter ureafaciens neuraminidase which has been reported recently as being an adequate enzyme to hydrolyze ganglioside GM1 as a substrate.

Animals↗
PubMed1982

Interactions of ganglioside GM1 with human and fetal calf sera. Formation of ganglioside-serum albumin complexes.

The interactions of ganglioside GM1 with human and fetal calf sera were studied, the following main results being obtained: (a) GM1, upon incubation with both sera gave origin to two GM1-protein complexes, which also occurred after interaction of GM1 with the albumin fractions prepared from the same sera. Instead no complex formation occurred using the albumin-free fractions. Therefore GM1 appeared to specifically bind serum albumin and to form GM1-albumin complexes. (b) GM1 binding to serum albumin started at ganglioside concentrations surely micellar (above 10(-6) M), was time and concentration dependent, and resulted in a relevant degree of GM1 complexation (up to 80% of total GM1 in human serum and up to 18% in fetal calf serum). (c) the binding kinetics appeared, in both serum and the correspondent albumin fraction, to be biphasic: in the first phase, occurring till about 2 . 10(-4) M GM1, the ratio between bound and total GM1 increased linearly with increasing GM1 concentration; in the second phase, occurring above 2 . 10(-4) M, the ratio remained practically constant. After these findings it should be expected that GM1, when present in serum containing systems, forms complexes with albumin. This should be approximately considered when studying the effects of exogeneous GM1 in in vivo and in vitro (tissue cultures) systems.

Animals↗
PubMed1985

High-resolution proton NMR studies of gangliosides. III. Elucidation of the structure of ganglioside GM3 lactone.

Ganglioside GM3 lactone (1) was prepared in 95% yield from the parent ganglioside by incubation at 25 degrees C for 4 days in glacial acetic acid. Inspection of the 500 MHz proton NMR spectra of 1 and its precursor in dimethylsulfoxide-d6-deuterium oxide at 30 degrees C revealed a large deshielding (+1.42 ppm) of the H-2 resonance of the galactosyl residue. This suggests that 1 must be the lactone formed by esterification of the sialic acid carboxyl group with the C-2 hydroxyl of the galactosyl residue. Consideration of all the NMR data leads to a specific structure proposal in which 1 has a highly rigid structure. Interesting features of the structure include a hydrophobic inner surface and a semicircular outer edge of seven-oxygen atoms, which may have physiological importance.

Chemical Phenomena↗
PubMed1990

Formation of a cytosolic ganglioside-protein complex following administration of photoreactive ganglioside GM1 to human fibroblasts in culture.

A GM 1 ganglioside derivative bearing a photoreactive nitrophenyl azide group and tritium labeled at the acetyl group of N-acetylneuraminic acid, has been administered to cultured human fibroblasts. With photolabeling experiments we found that a portion of the ganglioside in the cell cytosol was associated with a soluble protein of about 30 kDa.

Cells, Cultured↗
PubMed1985

Radioiodinated ganglioside GM1: a potential tool for the investigation of ganglioside function in vivo.

Ganglioside GM1 was labeled with 125I either directly or after conjugation to tyramine. Direct iodination of the sphingosine chain resulted in a compound which dehalogenated rapidly both in vitro and in vivo. The binding of the 125I[GM1-tyramine] conjugate to neuronal membranes in vitro was similar to that reported for 3H-GM1. The biodistribution of 125I activity after intravenous injection of 0.5 uM and 5 uM 125I[GM1-tyramine] in mice was also similar to that reported for 3H-GM1. This radioiodinated GM1 derivative might be useful for the study of ganglioside GM1 function in vivo.

Animals↗
PubMed1997

A synthetic approach to the c-series gangliosides containing sialyl-alpha(2-->8)sialyl-alpha(2-->8)sialic acid: synthesis of ganglioside GT4, alpha(2-->6) GT4 and GT3.

Trimeric sialic acid [Neu5Ac alpha(2-->8)Neu5Ac alpha(2-->8)Neu5Ac, 1] residue-containing gangliosides, GT4, alpha(2-->6)GT4 and GT3, have been synthesized for the first time. Methyl [phenyl] 5-acetamido-8-O-[5-acetamido-8-O-(5-acetamido-4, 7, 8, 9-tetra-O-acetyl-3, 5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylono-1", 9'-lactone)-4,7-di-O-acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylono-1',9-lactone]-4,7-di- O-acetyl -3,5-dideoxy-2-thio-D- glycero-D-galacto-2-nonulopyranosid]onate (3) was prepared from 1, via lactonization, methyl esterification of the carboxyl group at the reducting end, O-acetylation and conversion of the anomeric acetoxy group into a phenylthio group. Iodonium-promoted glycosylation of 3 with 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-beta-D-galactopyranoside (5), 2-(trimethylsilyl)ethyl 3-O-benzyl-beta-D-galactopyranoside (6), 2-(trimethylsilyl)ethyl 2-O-benzoyl-3-O-benzyl-beta-D-galactopyranoside (9), and 2-(trimethylsilyl)ethyl 2, 3-di-O-benzyl-beta-D-galactopyranoside (11) gave the corresponding tetrasaccharides (13-15, 17) having the (Neu5Ac)3-Gal structure. The peracylated oligosaccharides 18 and 24 derived from 13 and 17, and the previously reported lactose derivative 29 were converted into the alpha-trichloroacetimidates 20, 26 and 31, and coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (21) to afford the corresponding beta-glycosides 22, 27 and 32. These protected azidosphingosine derivatives were each transformed into the target gangliosides GT4, alpha(2-->6)GT4 and GT3 via selective reduction of the azido group, subsequent coupling with octadecanoic acid, O-deacylation and saponification of the methyl ester and lactone groups.

Carbohydrate Sequence↗
PubMed1988

Interactions of proteins with ganglioside-enriched microdomains on the membrane: the lateral phase separation of molecular species of GD1a ganglioside, having homogeneous long-chain base composition, is recognized by Vibrio cholerae sialidase.

The thermotropic behavior (studied by high-sensitivity differential scanning calorimetry) and susceptibility to Vibrio cholerae sialidase hydrolysis of large unilamellar vesicles of dipalmitoyl-phosphatidylcholine, containing native GD1a ganglioside or the molecular species of GD1a containing C18:1 or C20:1 long-chain base (C18:1 GD1a; C20:1 GD1a), were studied. Vesicles containing ganglioside (10% in molar terms) showed the presence in the heat capacity function of a second minor peak besides the phospholipid main transition peak. The presence of a second peak is much more evident with C20:1 GD1a than with C18:1 GD1a, the difference being potentiated by Ca2+ and indicating a different tendency of the CD1a molecular species to undergo lateral phase separation. The scans of vesicles containing native GD1a showed the features of those obtained with C18:1 GD1a and C20:1 GD1a, indicating that the main components of native GD1a, C18:1 GD1a and C20:1 GD1a, maintain their individual aggregative properties. V. cholerae sialidase affects vesicle-bound GD1a at a much higher rate (17-25-fold) than it does micellar GD1a, the activation by Ca2+ being 3- and 2-fold, respectively. The Vmax values were identical on C18:1 GD1a and C20:1 GD1a in micellar dispersions, whereas they were markedly higher (from 20 to 50%) on C18:1 GD1a than on C20:1 GD1a in vesicular dispersions. Exhaustive sialidase hydrolysis of vesicles carrying native GD1a produced C18:1 GM1 and C20:1 GM1 in the same proportion as the C18:1 and C20:1 species present in native GD1a (53.9% and 46.1%).(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture.

Cell density-dependent inhibition of growth and neural differentiation in the human neuroblastoma cell line SK-N-MC are associated with a ganglioside sialidase-mediated increase of GM1 and lactosylceramide at the cell surface. Because these glycolipids expose galactose residues, we have initiated the study of the potential role of galectins in such cellular events. Using specific antibodies, galectin-1 but not galectin-3 was found to be present at the cell surface. Assessment of carbohydrate-dependent binding revealed a saturable amount of ligand sites approaching 2.6 x 10(6) galectin-1 molecules bound/cell. Presence during cell culture of the sialidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid or of the GM1-binding cholera toxin B subunit effected a decrease of the presentation of galectin-1 ligands by 30-50%. The assumption that GM1 is a major ligand for galectin-1 was reinforced by the correlation between the number of carbohydrate-dependent 125I-iodinated GM1-neoganglioprotein binding sites and the amount of immunoreactive surface galectin-1, the marked sensitivity of probe binding to the presence of anti-galectin-1 antibody, and the inhibition of cell adhesion to surface-immobilized GM1 by the antibody. The results open the possibility that the carbohydrate-dependent interaction between ganglioside GM1 and galectin-1 may relay sialidase-dependent alterations in this cell system.

Cell Division↗
PubMed1992

The c-series gangliosides GT3, GT2 and GP1c are formed in rat liver Golgi by the same set of glycosyltransferases that catalyse the biosynthesis of asialo-, a- and b-series gangliosides.

Biosynthesis of the c-series gangliosides GT3, GT2 and GP1c was studied in Golgi derived from rat liver. Competition experiments show that the synthesis of ganglioside GT2 (GalNAc beta 1----4-(NeuAc alpha 2----8NeuAc alpha 2----8NeuAc alpha 2----3)Gal- beta 1----4Glc beta 1----1Cer) from GT3 (NeuAc alpha 2----8NeuAc alpha 2----8-NeuAc alpha 2----3Gal beta 1----4Glc beta 1----1Cer) seems to be catalysed by the same N-acetylgalactosaminyl-transferase (GalNAc-T), which converts GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----1Cer) to GM2 (GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1Cer). Similar competition experiments suggest moreover that the sialytransferase V (SAT V), which catalyses the synthesis of GT1a (NeuAc alpha 2----8NeuAc alpha 2----3Gal beta 1----3GalNAc beta 1----4- (NeuAc alpha 2----3)-Gal beta 1----4Glc beta 1----1Cer) from GD1a (NeuAc alpha-2----3Gal beta 1----3GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1-Cer) appears to be identical to the enzyme that catalyses the synthesis of GP1c (NeuAc alpha 2----8NeuAc alpha 2----3Gal beta 1----3-GalNAc beta 1----4(NeuAc alpha 2----8-NeuAc alpha 2----8NeuAc alpha 2----3)Gal beta-1----4Glc beta 1----4Glc beta 1----1Cer) from GQ1c (NeuAc alpha 2----3Gal beta 1----3Gal-NAc beta 1----4 (NeuAc alpha 2----8NeuAc alpha 2----8NeuAc alpha 2----3)Gal beta 1----4-Glc beta 1----1Cer).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Ganglioside GT1b in rat brain binds to p58, a brain-specific sodium-dependent inorganic phosphate cotransporter: expression cloning with a specific monoclonal antibody to ganglioside GT1b-binding protein.

To evidence the notion that gangliosides involve neuronal cell interactions in the brain, we surveyed the presence of ganglioside-binding proteins in membrane lysates of adult rat cerebellum. Three proteins (p58, p90, and p160) were identified as GT1b-binding proteins by incubation of the blot of the membrane lysate with GT1b micelles. We generated a monoclonal antibody (mAb) specific to the polypeptide portion of the GT1b-binding proteins (YAK-2). The YAK-2 mAb specifically reacted with all three proteins on blots of proteins pretreated under nonreducing conditions for SDS-PAGE, but reacted mainly with p58 under reducing conditions, showing that p90 and p160 are oligomeric forms of p58. The binding activity of the YAK-2 mAb was completely inhibited by the presence of GT1b micelles, indicating the specificity of YAK-2 mAb for p58 and its oligomers. Immunohistochemical investigations revealed that both p58 and GT1b colocalize within the granular layer of adult rat cerebellum. Expression cloning of p58 cDNA was performed using YAK-2 mAb, and five putative clones were obtained. Among them, the nucleotide sequence of one cDNA completely matched that of rat brain-specific sodium-dependent inorganic phosphate cotransporter (rBNPI), a 61 kDa membrane protein. COS7 cells were transfected with a Flag-chimeric construct containing the rBNPI/p58 cDNA, and the membrane lysate was subjected to immunoprecipitation with anti-Flag antibody. One protein (64 kDa) was detected only with YAK-2 mAb, and the membrane lysate specifically bound to GT1b micelles. Taking together, we propose that rBNPI/p58 functions as a GT1b-binding protein in neuronal cells.

Animals↗
PubMed1982

Incorporation of a ganglioside and spin-labeled ganglioside analogue into cell and liposomal membranes.

When an aqueous solution of a spin-labeled "two tail" gangliosidoid was incubated with liposomes or sheep erythrocytes, the broad single resonance line in the ESR spectrum disappeared and a signal showing an anisotropic motion appeared, indicating that the spin-labeled "two tail" gangliosidoid in the micellar state was transferred to the lipid phase of the acceptor membranes. The transfer was temperature- and time-dependent, irrespective of the acceptor membranes, indicating that the rate of transfer is determined by the escape of monomers from the micelles. The kinetics and temperature-dependence of the association of ganglioside II3NeuAc-GgOse4Cer with sheep erythrocytes was very similar to that of the "two tail" gangliosidoid, indicating that parts of ganglioside II3NeuAc-GgOse4Cer could be incorporated into the lipid phase of membranes via a similar mechanism.

Animals↗
PubMed1990

Ultrastructural localization of gangliosides, calcium and a high-affinity Ca(2+)-ATPase in nerve terminals: a contribution to the possible functional role of gangliosides.

By means of newly developed electron microscopical techniques (electron spectroscopic imaging, ESI; electron energy loss spectroscopy, EELS; immunogold labelling) a specific accumulation of endogenous calcium within the synaptic cleft and a distinct localization of a high-affinity Ca(2+)-ATPase at the inner sides of the pre- and postsynaptic membrane of nerve cells from fish brain have been demonstrated. Additionally, a differentiation-dependent expression of polysialoganglioside epitopes on the outer surface of nerve terminals in clustered arrangements was demonstrated using their ultracytochemical detection by means of the monoclonal antibody Q211. These results which are in agreement with parallel biochemical investigations on modulatory effects of exogenous gangliosides on a high-affinity Ca(2+)-ATPase in the CNS of vertebrates support our hypothesis that Ca(2+)-ganglioside complexes act as modulators for the processes of synaptic transmission and long-term neuronal adaptations.

Animals↗
PubMed1988

Biochemical and immunochemical analysis of gangliosides of human small cell lung carcinoma: production of monoclonal antibodies against a unique marker of small cell lung carcinoma, ganglioside Fuc GM1.

Immunization of mice with a pure preparation of the ganglioside adsorbed on Salmonella typhimurium and hybridization of splenocytes with myeloma P3-X63-Ag 8.653 have resulted in hybridomas producing monoclonal antibodies against ganglioside Fuc GM1, a marker of human small cell lung carcinoma. Characterization of four hybridomal clones and data on the antigenic specificity of the monoclonal antibodies are given. All four monoclonal antibodies reacted only with Fuc GM1 in an enzyme-linked immunosorbent assay. In radioimmunodetection of the antigen on thin-layer plates, two of the four monoclonal antibodies gave cross-reactions with Fuc GD1b. The obtained monoclonal antibodies have revealed the presence of Fuc GM1 in all seven cases of small cell lung carcinoma we have studied and the absence of Fuc GM1 in the normal human lung tissue and in lung adenocarcinomas.

Antibodies, Monoclonal↗
PubMed1986

Incorporation and degradation of GM1 ganglioside and asialoGM1 ganglioside in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency.

The uptake and degradation of GM1 ganglioside (GM1) and asialoGM1 ganglioside (GA1) were studied in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency, using the lipid-loading test. The glycolipids were incorporated from the media into the fibroblasts and the terminal galactose was hydrolyzed in normal cells. The hydrolysis rates of GA1 were 80-86% of normal on the 3rd day after loading, while GM1 was hydrolyzed slowly; 35-54% on the 14th day. In infantile GM1 gangliosidosis and I-cell disease, little GM1 and GA1 was hydrolyzed on any day of culture, while fibroblasts from patients with adult GM1 gangliosidosis, Morquio disease type B and galactosialidosis hydrolyzed the lipids at nearly normal rates. The intracellular accumulation of the glycolipids, on the basis of protein content, was abnormally high in the case of infantile GM1 gangliosidosis and I-cell disease, but normal in the other disorders examined. These observations indicate that the in situ metabolism of GM1 and GA1 is probably normal in fibroblasts from patients with adult GM1 gangliosidosis, Morquio disease type B and galactosialidosis, although in vitro beta-galactosidase activities in these disorders are very low. The results are compatible with findings that GM1 and GA1 do not accumulate in the somatic organs of patients with adult GM1 gangliosidosis and galactosialidosis. In I-cell disease, however, the results of the loading test did not agree with the finding that there is little accumulation of glycolipids in postmortem tissues.

Adult↗
PubMed1976

[Mouse brain gangliosides during development: demonstration of a new ganglioside].

The study of gangliosides as a function of age indicates that four of the main components GD1a (G3), GD1b (G2), GT1 (G1) and GQ (G0) are present at birth. They increase with age. On thin-layer chromatography, GD1a seems to be maximum at 18 days and GD1b continues to increase. GM1 increases also from birth to adult age. A new ganglioside has been detected in Mouse brain during its development. Not detected 5 days after birth, it is present at 18 days and in maximal quantity at adult age. This compound does not seem to be correlated to myelination process.

Age Factors↗
PubMed1978

[Study of gangliosides in normal (C57B1/6J) and quaking mice. Presence and characterization of a labile ganglioside in alkaline solution].

In the adult Quaking mutant, there is an increase in some polysialogangliosides (GT1 and Gq) and a 50% decrease in BM1 content. Thus, the latter ganglioside, which is a constituent of mature myelin, could be linked to one of the late steps of the myelination process. A novel ganglioside ALG1, which appears during the postnatal development of brain, has been isolated and purified; it contains an alkali labile linkage and after alkaline treatment yields GT1b. Comparison between normal Mice and Quaking mutants does not show any significant quantitative differences, under our conditions. At the stage at which it appears, it could be linked to steps of brain maturation other than myelimation.

Animals↗