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At least 1,207 records · Page 67Linked to original sources
PubMed1989

JONES ganglioside expression on retinal glia increases after axotomy.

The monoclonal antibody JONES recognizes a small group of gangliosides. Within the visual system of the adult rat JONES gangliosides are found only in those regions where neuronal regeneration is known to occur, i.e. the unmyelinated retina and optic nerve head. A transient increase in JONES ganglioside expression could be observed in the retinae of adult rats after optic nerve axotomy or in the retinae of animals receiving autologous sciatic nerve grafts. The highest levels of gangliosides identified by JONES were observed five days after surgery--contemporaneous with the maximum regenerative response of the adult rat retina after crush lesions. By double-labelling experiments using antibodies against glial cell markers--glial fibrillary acidic protein, S-100 and vimentin in conjunction with JONES-JONES gangliosides were shown to be expressed on retinal glial cells in vivo and in vitro. Elimination of glial cells by intraocular injection of aminoadipic acid abolished JONES labelling in vivo.

2-Aminoadipic Acid↗
PubMed1987

Complexity of the influence of gangliosides on histamine release from human basophils and rat mast cells.

The influence of exogenous addition of gangliosides on histamine release from human basophils and rat mast cells was examined in vitro. Gangliosides dose-dependently inhibited histamine release, and this inhibition was dependent on the ganglioside sialic acid content, since GT1b, having 3 sialic acid moieties, was more potent than gangliosides with 2 moieties (GD1a and GD1b), which again were more potent inhibitors than GM1 with one moiety. Asialo-GM1 was without effect. In high concentrations the gangliosides potentiated basophil histamine release. The modulation of histamine release was reflected in the sensitivity of the cells to extracellular calcium, since inhibition of the release could be counteracted by increasing the extracellular concentration of calcium.

Animals↗
PubMed1978

Composition and synthesis of three higher ganglioside homologs in bovine mammary tissue.

Three higher gangliosides were identified as constituents of bovine mammary gland. The structures of these three gangliosides were shown to be ceramide-glucose-galactose-(sialic acid)-N-acetylgalactosamine-galactose, ceramide-glucose-galactose-(sialic acid)2-N-acetylgalactosamine, and ceramide-glucose-galactose-(sialic acid)2-N-acetylgalactosamine-galactose. These gangliosides accounted for only a small fraction (less than 20%) of the lipid-bound sialic in mammary gland. White fatty acids with even carbon numbers from C14 to C26 were predominant in these gangliosides, they also contained C23 and C25 fatty acids. Mammary gland Golgi apparatus-rich fractions had all glycosyltransferases required for synthesis of these gangliosides starting with ceramide.

Animals↗
PubMed1991

Maternal protein deficiency in rat: effects on central nervous system gangliosides and their catabolizing enzymes in the offspring.

Maternal protein deficiency imposed on rats a month prior to conception, and during gestation and lactation, resulted in a significant cell loss in cerebrum, cerebellum, brain stem and spinal cord of pups at weaning. The cerebellum was the most affected central nervous system (CNS) region; it contained only 25% of the normal cell number. Undernourished pups were also found to have a lower concentration of total gangliosides in cerebrum as compared to that of controls. However, the total ganglioside concentration was unaffected in the cerebellum, brain stem and spinal cord by maternal undernutrition. In all regions, undernutrition caused significant changes in the proportions of individual gangliosides; these alterations were region-specific. Sialidase, beta-galactosidase, beta-glucosidase, and beta-hexosaminidase, which are involved in the catabolism of gangliosides, showed higher activities in all the regions of undernourished pups, suggesting that these enzymes may play a role in maintaining the porportions of various ganglioside fractions.

Animals↗
PubMed2005

Pathophysiological implication of ganglioside GM3 in early mouse embryonic development through apoptosis.

Apoptosis may occur in early embryos where the execution of essential developmental events has failed, and gangliosides, sialic acid-conjugated glycosphingolipids, are proposed to regulate cell differentiation and growth. To evaluate the regulatory roles of ganglioside GM3 in early embryonic development, this study examined its expressional patterns in apoptotic cells during early embryonic development in mice. Pre-implanted embryos were obtained by in vitro fertilization, which were treated at the 4-cell stage with three the apoptosis inducers, actinomycin D, camptothecin and cycloheximide, for 15 h. All three inducers significantly increased the percentage of apoptotic cells, as measured using a TUNEL method, but remarkably reduced the total cell numbers. The numbers of morula and blastocyst stages were significantly decreased by treatment of the embryos with the three apoptosis inducers compared with the control, with a similar result also observed in the number of blastomeres. Staining of early embryos with Hoechst 33342 revealed a significant percentage of apoptotic nuclei. Prominent immunofluorescence microscopy revealed a significant difference in the ganglioside GM3 expression in apoptotic embryos compared with the control, and RT-PCR also demonstrated a dramatic increase in ganglioside GM3 synthase mRNA in the apoptotic embryos. These results suggest that ganglioside GM3 may be pathophysiologically implicated in the regulation of early embryonic development through an apoptotic mechanism.

Animals↗
PubMed1993

Ganglioside GM1 protects cAMP 3'5':phosphodiesterase from inactivation caused by lipid peroxidation in brain synaptosomes of rats.

The preincubation of synaptosomes with nanomolar concentrations of ganglioside GM1 was shown to protect Ca(2+)-dependent and Ca(2+)-independent cyclic nucleotide phosphodiesterase from inactivation caused by lipid peroxidation (LPO) induction. Thus, Ca(2+)-dependent phosphodiesterase activity decreased to approximately 34% of the initial value following 30 min of LPO induction, but it constituted more than 60% of the control activity if synaptosomes were preincubated with 10(-8)M GM1, the difference being statistically significant. 10(-6)M alpha-tocopherol had a similar effect. As far as the lipid matrix is concerned, gangliosides were found to prevent to a great extent malonic dialdehyde (MDA) accumulation and to protect polyenoic fatty acids from oxidative destruction. The ability of gangliosides to protect phosphodiesterase from inactivation caused by LPO induction appears to be owing not only to the inhibition of the accumulation of LPO products, but to the direct activation of the enzyme as well, 10(-7) M of ganglioside GM1 having the maximal activating effect. In contrast to alpha-tocopherol and other antioxidants reacting directly with free radicals, the inhibitory effect of gangliosides appears to be mediated by signal transduction systems.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Exogenous application of gangliosides changes the state of excitability of retinal tissue as demonstrated by retinal spreading depression experiments.

Gangliosides are amphiphilic, sialic acid-containing glycosphingolipids which are found preferentially in complex composition in the cellular membranes of the nervous system of vertebrates, including the vertebrate retina as well as in other membranes. They are always exposed to the extracellular side of the membranes. By virtue of the negative charges they carry at their headgroup, they contribute to the surface charge of the membrane and may affect ion distribution, mainly that of protons and calcium ions, at the outer side of the membranes. Using retinal spreading depression (RSD) as a tool, we show in this study that the addition of exogenous gangliosides to the extracellular space can change the state of excitability of the retinal tissue. In RSD experiments it reduces the propagation velocity as well as the intrinsic optical signal of RSD waves. These effects are concentration dependent (IC50 about 20 microM) and increase with the increasing negative charge of the ganglioside headgroup. As a possible mechanistic basis of the changes found, the change of the calcium homeostasis of the extracellular space by the exogenously added gangliosides is discussed. Gangliosides have been reported to be useful in the treatment of some neuropathological syndromes, including migraine, although experimental verification has not been possible up to now. Taking into account that the retina is a true part of the CNS, our data may be interpreted as the requested verification.

Animals↗
PubMed2004

Interactions between gangliosides and proteins in the exoplasmic leaflet of neuronal plasma membranes: a study performed with a tritium-labeled GM1 derivative containing a photoactivable group linked to the oligosaccharide chain.

Interactions between gangliosides and proteins at the exoplasmic surface of the sphingolipid-enriched membrane domains can be studied by ganglioside photolabeling combined with cell surface biotin labeling. In the present paper, we report on the results obtained using a novel radioactive photoactivable derivative of GM1 ganglioside, carrying the photoactivable nitrophenylazide group at the external galactose. After cell photolabeling with the radioactive photoactivable derivative of GM1 and cell surface biotin labeling, sphingolipid-enriched domains were prepared from rat cerebellar neurons differentiated in culture and further purified by immunoprecipitation with streptavidin-coupled beads. Among proteins belonging to the sphingolipid-enriched domains that were biotin labeled, thus bearing an exoplasmic domain, a few were also cross-linked by the radioactive photoactivable ganglioside. In particular, two protein bands showing apparent molecular mass of 135 and 35 kDa were intensely photolabeled. The 135 kDa protein was immunologically identified as the GPI-anchored neural cell adhesion molecule TAG-1. These data suggest that hydrophilic interaction between the exoplasmic domains of the protein and the ganglioside sialooligosaccharide chain could exist.

Animals↗
PubMed2003

Chemical and enzymatic transacylation of amide-linked FA of buttermilk gangliosides.

The goal of this work was to alter the composition of amide-linked FA of bovine buttermilk gangliosides, particularly the disialoganglioside GD3, to adjust lipid sources to special food specifications and pharmacological or cosmetic applications. The chemical transacylation of amide-linked FA of buttermilk gangliosides with free arachidic acid (20:0) by a combination of basic hydrolysis and diethylphosphorylcyanide/triethylamine-catalyzed reacylation was compared to an enzymatic sphingolipid ceramide N-deacylase (EC 3.5.1.23)-catalyzed FA exchange by GC analysis and nano electrospray ionization-MS. The buttermilk predominantly contained the disialoganglioside GD3 and the monosialoganglioside GM3. The heterogeneity of FA that are incorporated into gangliosides, mainly palmitic acid (29.4 wt%), stearic acid (16.9 wt%), oleic acid (17.8 wt%), and myristic acid (8.5 wt%), was effectively altered by both transesterification techniques. Arachidic acid, which was not integrated into the initial buttermilk gangliosides, was transacylated to total gangliosides with 23.2 wt% (GD3, 6.7 wt%) by the chemical process and with 8.7 wt% (GD3, 13.8 wt%) when catalyzed enzymatically. Mainly behenic acid and lignoceric acid of GD3 were exchanged chemically, and stearic acid was exchanged by the enzymatic process. This observation might depend on hydrolytic sensitivities of amide-linked very long chain saturated FA or specific enzyme subtrate affinities, respectively. Results of chemical hydrolysis indicated there was a risk of sialic acid decomposition and unspecific degradations. Regarding specificity and avoidance of critical agents, the enzymatic transesterification is recommended for industrial-scale production of consumer goods.

Acylation↗
PubMed1985

Procedure for isolation of gangliosides in high yield and purity: simultaneous isolation of neutral glycosphingolipids.

While several methods for ganglioside extraction and isolation have been described, relatively little attention has been given to the effectiveness of separation from peptides, phospholipids, and various low-molecular-weight contaminants. A procedure is described for isolation of gangliosides in high purity and good yield from 1- to 400-mg samples (wet wt). A key step was mild acidification following homogenization, designed to dissociate gangliosides from lipophilic peptides which coextracted into organic solvents. This has proved particularly helpful for myelin and myelin-containing tissues (e.g., white matter, nerve) whose proteins have presented special problems in ganglioside isolation. In this study isolation was effected by consecutive chromatographies on Sephadex LH-20, DEAE-Sephadex, and silica gel following the initial acidification. The method applied to bovine white matter gave tissue concentrations (calculated from yields and radiolabeled tracer recoveries) that were similar to those obtained with three previously described procedures; however, peptide contaminants were an order of magnitude lower. Removal of low-molecular-weight contaminants, including nucleotide sugars, was virtually complete. In addition to ganglioside isolation the method can be used to obtain neutral glycosphingolipids as well. It is believed to have broad applicability to a diversity of tissues.

Animals↗
PubMed1984

Monoclonal antibody A2B5 reacts with many gangliosides in neuronal tissue.

Monoclonal antibody A2B5, clone 105, obtained from a mouse immunized with 8-day chicken embryo retinas, reacts with most neuronal cells in chicken retina as revealed by immunofluorescence studies [G.S. Eisenbarth, F.S. Walsh, and M. Nirenberg (1979), Proc. Natl. Acad. Sci. USA 75: 4913-4917]. The antibody binds to many antigens, presumably gangliosides, present in ganglioside fractions from chicken brain, chicken retina, and human brain, as detected by autoradiography of thin-layer chromatograms. Most of the antigens, which are found in the mono-, di-, tri-, and polysialoganglioside fractions, do not correspond in chromatographic mobility to any of the major gangliosides of these tissues, as revealed by orcinol reagent. Apart from the fact that only one neuraminidase-labile sialyl residue is required for binding, the carbohydrate sequence recognized by the antibody is not known. There is a qualitative and quantitative change in the ganglioside antigens in chicken brain and retina during development. The less sialylated antigens appear first, followed by the more sialylated ones. The adult tissues contain little ganglioside antigen.

Aging↗
PubMed1985

A new ganglioside in human meconium detected by antiserum against the human milk sialyloligosaccharide, LS-tetrasaccharide b.

Antibodies directed against human milk sialyloligosaccharides [D. F. Smith and V. Ginsburg (1980) J. Biol. Chem. 255, 55-59] are used to identify human meconium gangliosides by radioimmuneoverlay-thin-layer chromatography or by direct binding on nitrocellulose filters of sialyl[3H]oligosaccharide alditols obtained from gangliosides after ozonolysis and alkali-fragmentation. Thin-layer chromatograms of meconium monosialylgangliosides immunostained with rabbit antisera specific for LS-tetrasaccharide c (NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc) or LS-tetrasaccharide b (Gal beta 1-3[NeuAc alpha 2-6]GlcNAc beta 1-3Gal beta 1-4Glc) reveal their corresponding gangliosides, 6'-LM1 and a previously undescribed ceramide derivative of LS-tetrasaccharide b, respectively. The sialyl[3H]oligosaccharides derived from the monosialylganglioside fraction of meconium are separated by paper chromatography and assayed for binding to specific anti-sialyloligosaccharide sera. Antisera specific for LS-tetrasaccharide c and 3'-sialyllactose (NeuAc alpha 2-3Gal beta 1-4Glc) identify their corresponding 3H-labeled haptens released from the major meconium gangliosides 6'-LM1 and GM3, respectively. Binding of a ganglioside-derived sialyl[3H]oligosaccharide by anti-LS-tetrasaccharide b serum is consistent with the presence in meconium of a monosialylganglioside with the following proposed structure: (formula; see text)

Gangliosides↗
PubMed1985

Tetanus toxin interaction with human erythrocytes. II. Kinetic properties of toxin association and evidence for a ganglioside-toxin macromolecular complex formation.

The properties of tetanus toxin interaction with human erythrocytes supplemented with disialo- and trisialo-gangliosides have been investigated. Binding of toxin is linear with time for 1 h and is 3-4-fold higher at 37 degrees C than at 4 degrees C during incubation of long duration. It exhibits saturation at toxin concentrations between 0.1 and 1 microgram/ml; however, it is nonsaturable between 1 and up to 50 micrograms/ml. It is effectively prevented by free gangliosides and antibodies or by pretreatment with sialidase but is unaffected by a number of closely related ligands including toxoid and toxin fragments. NaCl (1 M) removes a great portion (86%) of cell-associated toxin while Triton X-100 extracts an additional fraction (30%) of the salt-resistant cell-bound toxin. The residual sequestred toxin after detergent extraction is sensitive to proteolytic degradation. The trypsin-stable fraction (1.5%) is biotoxic and may be indicative of internalization of toxin. A macromolecular complex of about 700 kDa containing toxin and gangliosides has been isolated and characterized by Sephacryl S-300 gel permeation chromatography, SDS-gel electrophoresis, immunoprecipitability and biotoxicity. This complex is obtained only in ganglioside-supplemented cells and not when free 3H-labeled GD1b is reacted with 125I-labeled toxin in solution in the absence of cells. The hydrophobicity properties acquired as a result of ganglioside-toxin interaction, presumably at the cell surface, suggest a conformational change of the toxin which may enable its penetration into the bilayer.

Binding, Competitive↗
PubMed1985

Gangliosides reduce leakage of aqueous-space markers from liposomes in the presence of human plasma.

We have studied the role of glycolipids in reducing leakage of aqueous-space markers from liposomes, composed primarily of egg phosphatidylcholine, in the presence of human plasma. Liposomes were either small unilamellar (SUV) or large unilamellar (LUV). Leakage of liposome contents as affected by the incorporation into the liposomal bilayer of mono-, di-, or trisialogangliosides (GM, GD, GT) at different molar ratios in the presence or absence of cholesterol was examined. Leakage from liposomes decreased with increasing ganglioside sialic acid. Asialogangliosides had no effect on calcein leakage in the presence of plasma. The stabilizing effect of gangliosides and cholesterol was synergistic, and SUV containing 10 mol% GT and 33 mol% cholesterol had a half-life for leakage of calcein in plasma at 37 degrees C approaching 24 hours. LUV in the presence of plasma retained their contents longer than SUV, and gangliosides had an additional stabilizing effect. Phosphatidylserine and sulfatides were also capable of substituting for gangliosides in stabilizing liposomes to plasma-induced leakage. It appears that gangliosides stabilize liposomes in plasma at least in part through their ability to impart surface negative charge.

Blood Proteins↗
PubMed1975

Gangliosides of the human gastrointestinal mucosa.

Gangliosides of the human alimentary mucosa were purified and analysed with thin-layer chromatography and gas chromatography. The content of ganglioside neuraminic acid was 0.16 mumol/g dry weight in the stomach, 0.07 mumol/g dry weight in the small intestine and 0.11 mumol/g dry weight in the large intestine. Mono- and disialosylhemosides were the major gangliosides, on a molar basis 68% of the total found in the stomach and 44% of the total in the small and large intestine. Considerable amounts of more complex gangliosides were found, especially in the small and large intestine, in which the molar content of tri- and tetraglycosylgangliosides containing galactosamine made up 38% of the total. Two glucosamine-containing gangliosides were also found, the probable structures of which were mono- and disialotetraglycosylceramide. The presence of the latter is reported for the first time.

Cerebrosides↗
PubMed1976

Characterization of two gangliosides from human leukemic polymorphonuclear leukocytes.

Eight bands of gangliosides, from human polymorphonuclear leukocytes were demonstrated by thin-layer chromatography. Bands 4 and 5 were isolated and purified in sufficient amounts to allow their biochemical identification by thin-layer chromatography, gas chromatography and sequential action of glycosidases and neuraminidase. The major ganglioside was characterised as N-acetylneuraminylgalactosyl-beta-N-acetylglucosaminyl-beta-galactosyl-beta-glucosylceramide. A second ganglioside was tentatively identified as N-acetylneuraminyl-galactosyl-beta-N-acetylglucosaminyl-beta-(N-acetylneuraminyl)galactosyl-beta-glucosylceramide. Both gangliosides isolated were hydrolysed by neuraminidase. However, treatment of the intact cells with neuraminidase did not alter the ganglioside pattern.

Carbohydrates↗
PubMed1976

Neuraminic acid-specific modification and tritium labelling of gangliosides.

1. A crude ganglioside mixture and pure GM1 and GD1a from bovine brain grey matter were prepared on a large scale. 2. The C7- and G8-analogues of NeuNAc were prepared from Collocalia mucoid and their structures established by gas-liquid chromatography and mass spectrometry. 3. Using model compounds in addition to various gangliosides, the conditions for the periodate oxidation and subsequent borohydride reduction of gangliosides were investigated with regard to the yield of C7- and C8-analogues of NeuNAc and the integrity of other monosaccharides in the oligosaccharide chain. These conditions were optimised to yield maximum C8-NeuNAc production and low C7-NeuNAc formation. Thus products were obtained which closely resemble the native gangliosides. 4. Using boro [3H] hydride, ganglioside derivatives with high specific radioactivity were prepared for the first time, containing either NeuNAc and labelled C8-NeuNAc or mainly labelled C7-NeuNAc depending on the prevailing conditions.

Animals↗
PubMed1983

A new family of fucose-containing gangliosides isolated from human senile cataracts.

Gangliosides were isolated from human cataracts by solvent extraction, silicic acid chromatography, thin-layer chromatography and gas-liquid chromatography. A total of 11 resorcinol-positive bands were revealed by thin-layer chromatography. Bands 1, 5 and 7 were partially identified as hematoside. GM1 ganglioside and disialoganglioside by gas-liquid chromatography as the O-trimethylsilylated methylglycosides. In addition to galactose and glucose, fucose was found to be present in seven ganglioside fractions (bands 3, 4, 6 and 8-11). All these fucolipids contained N-acetylglucosamine in addition to sialic acid. Fucogangliosides G-3, G-4 and G-6 contained a 2:1 molar ratio of galactose to glucose, while G-8 had a galactose/glucose molar ratio of 1:1. Long-chain fatty acids constituted 60-77% of the total normal fatty acids in N-acetylgalactosamine-containing gangliosides, whereas the fucogangliosides contained primarily palmitate, although significant amounts of long-chain acids were also detected. The major long-chain base of the fucoganglioside was sphinganine (dihydrosphinogosine). The role of fucose-containing gangliosides in maintaining adhesions between lens membranes in cataracts is discussed with reference to glycosphingolipids in other tissues.

Cataract↗