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PubMed1992

Ganglioside alterations in YAC-1 cells cultivated in serum-supplemented and serum-free growth medium.

Gangliosides of the 'GM1b-pathway' (GM1b and GalNAc-GM1b) have been found to be highly expressed by the mouse T lymphoma YAC-1 grown in serum-supplemented medium, whereas GM2 and GM1 ('GM1a-pathway') occurred only in low amounts [Müthing, J., Peter-Katalinić, J., Hanisch, F.-G., Neumann, U. (1991) Glycoconjugate J 8:414-23]. Considerable differences in the ganglioside composition of YAC-1 cells grown in serum-supplemented and in well defined serum-free medium were observed. After transfer of the cells from serum-supplemented medium (RPMI 1640 with 10% fetal calf serum) to serum-free medium (RPMI 1640 with well defined supplements), GM1b and GalNAc-GM1b decreased and only low amounts of these gangliosides could be detected in serum-free growing cells. The expression of GM1a was also diminished but not as strongly as that of GM1b and GalNAc-GM1b. These growth medium mediated ganglioside alterations were reversible, and the original ganglioside expression was achieved by readaptation of serum-free growing cells to the initial serum-supplemented medium. On the other hand, a 'new' ganglioside, supposed to represent GalNAc-GD1a and not expressed by serum-supplemented growing cells, was induced during serum-free cultivation, and increased strongly after readaptation. These observations reveal that the ganglioside composition of in vitro cultivated cells can be modified by the extracellular environment due to different supplementation of the basal growth medium.

Animals↗

PubMed1984

Behavior of sugar derivatives in procedures for ganglioside isolation.

A common method of studying ganglioside metabolism is to measure the amounts of radioactivity incorporated into ganglioside from a radiolabeled precursor. This requires that radioactive nonganglioside material be completely removed from the ganglioside fraction. Nucleotide sugars and aminosugars comprise an important source of such contaminants. Therefore, we have studied their behaviors in several procedures currently employed to isolate gangliosides. Over 50% of the radioactivity associated with several nucleotide sugars added to a brain homogenate is extracted with chloroform/methanol (2:1, v/v), and most of this is recovered in the upper phase of a Folch partition. Dialysis against water removes almost all of the free aminosugar but only 70% of nucleotide sugar. Treatment with alkaline phosphatase, phosphodiesterase and alkaline methanol followed by dialysis removes almost all of the nucleotide diphosphate sugars but only 88% of cytidine 5'-monophosphate sialic acid (CMP-NeuAc). Nucleotide sugars cannot be separated from gangliosides by Unisil or Iatrobead chromatography, but nucleotide diphosphate sugars and gangliosides are resolved with Sephadex LH-20 chromatography following treatment with phosphodiesterase and alkaline phosphatase. CMP-NeuAc was not satisfactorily separated from gangliosides using any of the procedures.

Brain Chemistry↗

PubMed1992

Effect of prenatal and postnatal exposure to ethanol on rat central nervous system gangliosides and glycosidases.

We investigated the effect of maternal alcohol consumption on cell number, gangliosides and ganglioside catabolizing enzymes in the central nervous system (CNS) of the offspring. Virgin female rats of the Charles Foster strain were given 15% (v/v) ethanol in drinking water one month prior to conception and during gestation and lactation. At 21 days postnatal age, the offspring were sacrificed and the brains were separated into cerebrum, cerebellum and brain stem to investigate possible regional variations. Compared to controls, wet weight of cerebrum, cerebellum and brain stem, and of spinal cord was decreased in the pups exposed to alcohol. DNA and protein contents were also found to be lowered in all the CNS regions of the pups exposed to alcohol. Conversely, maternal alcohol consumption was found to increase the concentration and the content of total ganglioside N-acetyl-neuraminic (NANA) in CNS of the pups. In addition, alcohol treatment was found to induce alterations in the proportions of individual ganglioside fractions. Interestingly, these alterations are somewhat different than those observed in the neonatal brain and spinal cord of the pups subjected to prenatal alcohol exposure. The alterations in the proportions of ganglioside fractions were shown to be region-specific. Maternal alcohol consumption resulted in decreased activities of sialidase, beta-galactosidase, beta-glucosidase and beta-hexosaminidase. The results suggest that the alcohol-associated increases in ganglioside concentration may be at least partly due to the decreased activities of ganglioside catabolizing enzymes.

Animals↗

PubMed1986

Regulation of liver cell ganglioside composition by extracellular fluid viscosity.

The viscosity of plasma and extracellular fluid has been shown to be a regulator of lipoprotein production both in cultured hepatocytes and in vivo. The possibility that this extracellular effect on cell function involves modulation of cell surface membrane components was examined. In the present work, we studied the effect of medium viscosity on liver cell gangliosides known to be involved in various membrane functions and to be located predominantly at the cell surface membrane. Cultivation of isolated hepatocytes as primary cultures markedly reduced the ganglioside content, but this reduction process was attenuated by increasing the viscosity of the culture medium. Elevation of extracellular fluid viscosity inhibited the degradation of the cell gangliosides and secretion of lysosomal enzymes involved in ganglioside degradation. The cellular activity of these enzymes as well as the activity of enzymes involved in ganglioside synthesis, CMP-NANA:GM1 sialyltransferase, CMP-NANAP:GM3 sialyltransferase and UDP-galactose:GD2 galactosyltransferase, were not affected by modulation of the extracellular medium viscosity. It is proposed that the modulation of cell ganglioside content by extracellular fluid viscosity is due to an effect on enzymes involved in ganglioside catabolism.

Acetylglucosaminidase↗

PubMed1999

Gangliosides and neutral glycolipids in ependymal, neuronal and primitive neuroectodermal tumors.

Neutral glycolipid and ganglioside compositions were determined on 11 ependymal tumors, 12 medulloblastomas, 6 other neuronal tumors of the brain, 4 peripheral neuroblastomas, 1 cerebral primitive neuroectodermal tumor (PNET), and 1 PNET of the thoracic wall. Within the group of tumors that can demonstrate neuronal phenotypes, there was an association between the degree of neuronal differentiation usually demonstrated by these tumors and the proportions of both GD1a and 1b-pathway gangliosides. The amount of globoside also correlated with the amount of 1b pathway gangliosides. Patients with medulloblastomas whose 1b gangliosides made up over 15% of the total gangliosides survived longer that those with lower proportions of 1b gangliosides. The only gangliosides in the choroid plexus papilloma were GM3 and GD1a, but other ependymal tumors had significant amounts of GD1b and its metabolic precursors. Ependymoma and anaplastic ependymoma had similar neutral glycolipid compositions, which were different from subependymoma, which lacked ceramide monohexoside and ceramide dihexoside. These differences in glycolipid compositions suggest that there may be fundamental biological differences between these types of ependymal tumors.

Adult↗

PubMedDate not supplied

Altered expression of ganglioside phenotypes of human gliomas in vivo and in vitro.

A library of epitope-defined antiganglioside monoclonal antibodies has been used to analyze the ganglioside phenotype of human glioma cell lines, rodent xenografts derived from them, and a separate panel of human glioma biopsies by multiple quantitative and qualitative assays. We have shown that the ganglioside phenotypes of cultured cell lines differ from the ganglioside phenotypes in the xenografts grown from the parent lines. The lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 are expressed in the majority of primary human central nervous system neoplasms and xenografts derived from glioma cell lines, whereas glioma cell lines themselves express 3'-isoLM1 and 3',6'-isoLD1 in only 2/15 and 0/15 cases, respectively. Examination of the ganglioside profiles of serially passaged xenografts established from the glioma cell line D-54 MG, which does not express the lacto series, revealed the appearance of these gangliosides within one to two passages in vivo. The presence of these defined gangliosides in the majority of human gliomas and their absence in normal brain supports their application in compartmental therapy of primary central nervous system tumors.

Animals↗

PubMed1991

Ganglioside levels in hypoxic brains from neonatal and premature infants.

In this study, 13 cases of newborn term-gestational infants and six cases of premature infants who died of hypoxia were selected for the determination of ganglioside levels in several regions of brains obtained at autopsy. Cases were divided into three groups according to the hypoxic interval and gestational age: Group A, six cases of newborn infants. The average time of hypoxia was 6.4 h. Group B, seven cases of newborn infants. The average time of hypoxia was about 71 h. Group C, six cases of premature infants. The average hypoxia time was 34.7 h. Frontal cortex, forebrain, hippocampus, and parahippocampal gyrus and cerebellum of each brain were examined. The method of Ladisch and Gillard (1985) was used to purify and quantify gangliosides. The results showed that total gangliosides decreased significantly in three regions of cerebral hemispheres of group B and in four brain regions of group C, as compared with group A (p less than 0.01). The amount of gangliosides in frontal cortex in group B was lower than in group C (p less than 0.01). The four major gangliosides (GM1, GD1a, GD1b, and GT1b) were all reduced in cerebral hemispheres of group B and C. In hypoxic brains, the percentage of gangliosides also showed some alterations. There was less GD1a in the cerebral hemispheres of group B and the frontal cortex of group C. The amount of GD1b was also less in the frontal cortex and forebrain of group B than in group A or C. The results suggest that severe hypoxia might cause decreases in brain gangliosides that correlate to the severity of brain damage.

Brain Chemistry↗

PubMed1999

Ganglioside profiles in human gliomas: quantification by microbore high performance liquid chromatography and correlation to histomorphology and grading.

The composition and the content of gangliosides changes during physiological growth and differentiation as well as in neoplastic cell transformation. In order to determine if ganglioside profiles correlate with brain tumour malignancy, the ganglioside distribution was determined in 31 gliomas of astrocytic origin and in non-tumour tissue by a recently developed microbore high performance liquid chromatography (HPLC) method. Glioma malignancy was graded according to the grading system proposed by the World Health Organization (WHO) in 1993. In general, an increase of GD3 and a decrease of normal brain gangliosides correlated with a higher grade of malignancy. Pilocytic astrocytomas Grade I had a distinctive ganglioside profile, histologically as well as biochemically. Although they are low-grade gliomas, the pilocytic astrocytomas exhibited a GD3 content comparable to anaplastic gliomas and could only be biochemically distinguished from other tumour grades by relatively high type "b" ganglioside levels. Thus, ganglioside composition not only reflects anaplasia but can also be used to indicate biological characteristics of tumours of different histogenetic origin.

Astrocytoma↗

PubMed2002

Ganglioside a/b ratio in different rat brain regions following chronic diazepam treatment.

Gangliosides are sialic acid-containing glycosphingolipids that play a variety of important functions in neurons. The main purpose of this study was to determine the a/b ratio of gangliosides in different rat brain regions (cerebral cortex, hypothalamus, caudate nucleus, hippocampus, thalamus and cerebellum) after prolonged diazepam treatment. Male Wistar rats were maintained on a nutritionally adequate diet and diazepam was administered in a dose of 10 mg/kg day for 180 days. Total gangliosides were extracted according to Harth and the total ganglioside-NeuAc content was determined by Svennerholm's resorcinol method, modified by Miettinen and Takki-Luukkainen. The a/b ratio remained unchanged in rat hypothalamus, thalamus and cerebellum. It was slightly decreased in the caudate nucleus and hippocampus, but this was not statistically significant. A drastic decrease ( p<0.01) in ganglioside content, compared to control animals, was found in rat cerebral cortex. Ganglioside a/b profile did not change significantly in most of the brain regions (except in cerebral cortex), which suggests that adaptive changes occurred upon prolonged exposure to diazepam, in order to maintain the physiological ratio of ganglioside a- and b-series in distinct brain areas.

Animals↗

PubMed1985

A solvent partition method for microscale ganglioside purification.

A simple and rapid method for the purification of gangliosides from the total lipid extract of plasma, cells, or tissue is described. The novel component of the method is the partition of the dried total lipid extract in the three-component solvent system consisting of diisopropyl ether, 1-butanol, and 50 mM aqueous NaCl (6/4/5, v/v/v). Gangliosides partition nearly quantitatively into the lower aqueous phase, and other lipids into the upper organic phase, resulting from the mixture of these three solvents. The ganglioside-containing aqueous phase is then freed of salts and other low-molecular-weight impurities by gel filtration. The thin-layer chromatographic patterns of total gangliosides thus obtained are clear and distinct, even when small samples with very low ganglioside concentrations (e.g., 1-ml samples of plasma) are processed by this method. Thus, this new ganglioside purification method is especially applicable to comparative qualitative studies of gangliosides requiring the analysis of multiple small samples.

1-Butanol↗

PubMed1986

Gangliosides indirectly inhibit the binding of laminin to sulfatides.

Laminin, a glycoprotein of basement membranes, agglutinates aldehyde-fixed erythrocytes. Laminin-mediated hemagglutination is strongly inhibited by some gangliosides and anionic phospholipids. Laminin, however, binds only to sulfatides among the lipids extracted from erythrocytes. We now report that gangliosides are remarkably potent inhibitors of laminin binding to sulfatides when both lipids are adsorbed on plastic. A 50% inhibition of laminin binding to 100 ng of sulfatides is obtained with 10 ng of GM3 and 8 ng of GM1, respectively. Mixing of sulfatides with neutral glycolipids, phosphatidyl choline, or cholesterol does not inhibit laminin binding, whereas mixing with sulfatide-depleted erythrocyte lipids enhances binding. Inhibition of binding by gangliosides is not due to competition for adsorption to the plastic, as preincubation of the adsorbed lipids with neuraminidase reverses inhibition by GM3, but not by GM1 which is not a substrate for the enzyme. These results are consistent with the observations that treatment of fixed erythrocytes with neuraminidase increases their agglutinability by laminin and that pretreatment of erythrocytes with gangliosides followed by washing gives similar inhibition as seen when gangliosides are present as competitive inhibitors. Thus, inhibition of laminin-mediated agglutination by gangliosides probably results from masking of erythrocyte sulfatides due to adsorption of gangliosides onto the membrane rather than from a direct competition for laminin binding sites.

Binding Sites↗

PubMed1978

A model for ganglioside behaviour in cell membranes.

Gangliosides from beef brain have been spin-labeled using two different attaching groups and employed to investigate the physical nature of ganglioside behaviour in membranes. Results obtained using EPR spectroscopy indicate that, in phosphatidylcholine bilayers at physiological pH, ganglioside oligosaccharide chains are quite mobile and show a measurable tendency towards cooperative interaction amongst themselves. We suggest that the source of this interaction is the formation of H-bonds between sugar residues in adjacent ganglioside molecules. We present evidence that physiological (extracellular fluid) levels of Ca2+ and Mg2+ lead to cross-linking and condensing of ganglioside headgroups by complexing sialic acid carboxyl residues. Ganglioside headgroup interactions are not very sensitive to changes in the buffer ionic strength, suggesting that ionic interactions are of minor importance. We have found no measurable tendency for headgroup carbohydrate to penetrate hydrophobic regions of lipid bilayers. EPR spectroscopy was also used to follow the interaction of spin-labeled gangliosides with the glycoprotein, glycophorin, and with intact BHK cells. We suggest that these carbohydrate-based interactions should contribute significantly to the properties of the eucaryotic cell glycocalyx. We predict that laterally mobile carbohydrate-bearing components of cell surface will show a tendency to cluster about complex glycoprotein arrays, especially if the species involved bear accessible carboxylic acid functions.

Animals↗

PubMed1984

Role of gangliosides in adhesion and conductance changes in large spherical model membranes.

The formation of two spherical model membranes at the tips of two syringes has allowed us to study the role of gangliosides in membrane adhesion and look for changes in conductance between two such membranes during the process of adhesion. Membranes were formed in aqueous 100 mM NaCl, 10 mM KCl, 1 mM CaCl2 from 1% (w/v) egg phosphatidylcholine in n-decane, with or without mixed bovine brain gangliosides. After thinning to the 'black' bilayer state, two membranes were moved into contact. With gangliosides, the contact area and conductance increased colinearly with time over a 5 to 20 min period of adhesion. The role of electrostatic bridging by calcium was investigated. In the absence of calcium or in the presence of 2 mM EDTA, adhesion proceeded after a longer lag time at about one-half the normal rate. As the ganglioside concentration was increased from 0 to 15 mol%, the electrical conductance of individual membranes decreased 3-fold from 48 +/- 30 nS/cm2 to 17 +/- 13 nS/cm2. The conductance was pH dependent with a minimum at neutral values. At neutral pH, when two membranes containing 4.1 mol% gangliosides adhered, the region of adhesion had a specific conductance three times that of the nonadhering regions of membranes. Without gangliosides, the specific conductance of the contact region was the same as that of non-adhering regions of the membrane. These data suggest that mixed gangliosides can mediate an adhesion-dependent increase in conductance.

Cell Adhesion↗

PubMed1994

Regulation by gangliosides and sulfatides of phospholipase A2 activity against dipalmitoyl- and dilauroylphosphatidylcholine in small unilamellar bilayer vesicles and mixed monolayers.

The modulation by gangliosides GM1 and GD1a, and sulfatide (Sulf) of the activity of porcine pancreatic phospholipase A2 was studied with small unilamellar vesicles of dipalmitoylphosphatidylcholine (L-dpPC) and lipid monolayers of dilauroylphosphatidylcholine (L-dlPC). The presence of Sulf always led to an increase of the maximum rate of the enzymatic reaction, irrespective on whether the vesicles were above, in the range of, or below the bilayer transition temperature. Sulf did not modify the latency period for the reaction that is observed at the bilayer transition temperature. Gangliosides inhibited the maximum rate of enzymatic activity bilayer vesicles in the gel phase but the effect was complex. When the reaction was carried out at a temperature within the range of the bilayer phase transition, the gangliosides inhibited the maximal rate of the reaction in proportion to their content in the bilayer. However, at the same time the latency period observed with vesicles of pure phospholipid at this temperature was shortened in proportion to the mole fraction of gangliosides in the bilayer. At temperatures above the bilayer phase transition, gangliosides stimulated the activity of PLA2. Preincubation of the enzyme with Sulf or gangliosides did not affect the activity against bilayer vesicles of pure substrate. These glycosphingolipids did not modify the rate or extent of desorption of the enzyme from the interface, nor the pre-catalytic steps for the interfacial activation of PLA2, or the enzyme affinity for the phospholipid substrate. Also, the activity of the enzyme was not altered irreversibly by glycosphingolipids. Our results indicate that Sulf and gangliosides modulate the catalytic activity of PLA2 at the interface itself, beyond the initial steps of enzyme adsorption and activation, probably through modifications of the intermolecular organization and surface electrostatics of the phospholipid substrate.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1976

Isolation and partial characterization of human kidney gangliosides.

1. Eight gangliosides were purified from chloroform/methanol extracts of human kidneys by using modified Folch partition, dialysis, ethanol precipitation, silicic acid column chromatography and preparative thin-layer chromatography. 2. By thin-layer chromatographic behaviour and gas-liquid chromatographic determinations the main gangliosides in human kidney are N-acetylneuraminyllactosylceramide (74% of total) and di-N-acetylneuraminyllactosylceramide (19% of total). 3. Five hexosamine-containing fractions were isolated. Four of them were homogeneous on thin-layer chromatography, and one contained two gangliosides. By gas-liquid chromatography-mass spectrometry it was shown that two gangliosides (together 5% of total) contain glucosamine, and one (1% of total) contains galactosamine. The other of the glucosamine gangliosides contains fucose in addition to the usual sugars found in gangliosides. Of the two remaining hexosamine positive fractions (together 1% of total) one was homogeneous on thin-layer chromatography, the other contained two gangliosides. These two fractions contained both glucosamine and galactosamine. 4. The main long-chain base in all fractions was sphingosine.

Chromatography, Gas↗

PubMed1980

A procedure for the quantitative isolation of brain gangliosides.

In a systematic study of the optimal conditions for the quantitative isolation of gangliosides from brain tissue and their further purification the yield of gangliosides obtained by extraction of the tissue twice with twenty volumes of chloroform/methanol/water (4 : 8 : 3, v/v) was larger than that obtained with all other solvents tested, including tetrahydrofuran/phosphate buffer. The gangliosides were separated from other lipids by phase partition, water was added to the total lipid extract to give a final chloroform/methanol/water volume ratio of 4 : 8 : 5.6. Isolation of gangliosides from the total lipid extract with the aid of anion-exchange resins was not practical as a routine procedure on a large scale. The crude gangliosides extract was freed from low molecular weight contaminants by dialysis against water. This method was superior to the purification on gel filtration media or on anion-exchange resins, which required large columns with selective losses of gangliosides as a result. The present method has been applied to human brain, and the concentration and distribution of gangliosides in the human forebrain in infancy and old age are given.

Aged↗

PubMed1986

Composition of gangliosides from ovine testis and spermatozoa.

Gangliosides were extracted and purified from ovine testis and ejaculated spermatozoa which contained, respectively, 57 and 9 nmol lipid-bound sialic acid per gram wet weight. Fourteen gangliosides were resolved by thin-layer chromatography of testicular gangliosides, of which eleven were purified in sufficient quantity to enable a complete compositional analysis of the carbohydrate residues to be performed. None of the gangliosides contained fucose, but several contained N-glycolylneuraminic acid as a component of the sialic acid species. Relative migration on thin-layer chromatograms relative to known standards, compositional analysis, and selective degradation by specific enzymes were used as the basis for identification. Testis contained members of the ganglio series (GM1, GD1a, GD1b, GT1b, GQ1b), hematoside series (GM3, GD3), and sialosylparagloboside in the molar ratio of 54:40:6, respectively. Testicular GM3, GM1, GD3, GD1a, GD1b and GT1b ran as double bands on thin-layer chromatography which could be accounted for by observed differences in the fatty acid moiety. In addition, the slower migrating band of each pair contained some or all of its sialic acid residues as N-glycolylneuraminic acid, whereas the faster migrating band contained exclusively N-acetylneuraminic acid, except for GM3 where N-acetylneuraminic acid was the sole species in both bands. Thin-layer chromatography of sperm gangliosides revealed seven bands comigrating with equivalent testicular gangliosides. These coincided with the slower migrating bands of testicular GM3, GM1, GD3, GD1a, both bands of GD1b, and possibly both bands of GT1b. Sperm contained only trace amounts of sialosylparagloboside but, in addition, two unidentified bands which were absent from testis were also observed. The molar ratio of the ganglio series to the hematoside series in sperm was 42:58 with GM3 accounting for 42% of total gangliosides.

Animals↗

PubMed1990

Gangliosides in the human glioma cell line U-118 MG grown in culture or as xenografts in nude rats.

This study was undertaken to characterize gangliosides in the human glioma cell line U-118 MG. The cell line was grown both in cell culture and as xenografts in nude rats. A common finding in both culture and xenograft cells was the high proportion of the lactoseries ganglioside 3'-LM1, approximately one third of the total ganglioside sialic acid. Otherwise, there were marked differences between the two cell sources. The cells grown in culture had a more simple ganglioside pattern than those grown in xenografts. In the latter instance, more complex gangliosides of the lactoseries, including 3'8'-LD1, sialyllactonorhexaosylceramide and a branched structure with two terminal NeuAc alpha 2-3Gal beta 1- 4GlcNAc chains, and the gangliotetraose series were found. Another marked difference involved GM2, which in the cultured cells was a major fraction, indicating that the synthesis of the gangliotetraose series gangliosides in the former stopped at the level of GM2. These results show that the ganglioside composition of a glioma cell line is strongly influenced by environmental factors.

Animals↗