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At least 19 recordsLinked to original sources
PubMed1977

The biosynthesis of brain gangliosides. Separation of membranes with different ratios of ganglioside sialylating activity to gangliosides.

Brain subcellular fractions were analysed for ganglioside-sialylating activity by measuring the incorporation of N-[3H]acetylneuraminic acid from CMP-N-[3H]acetylneuraminic acid into endogenous ganglioside acceptors (endogenous incorporation) and into exogenous lactosyceramide (haematoside synthetase activity). The ratios of endogenous incorporation to gangliosides and of haematoside synthetase to gangliosides for the synaptosomal and mitochondrial fractions from a washed crude mitochondrial fraction were lower than those obtained for other membrane fractions. The differences appear to reflect intrinsic characteristics of each membrane fraction. The results of labelling in vitro and the time course of labelling of gangliosides of the different subcellular fractions in vivo after injection of N-[3H]acetylmannosamine are consistent with the possibility of a subcellular site for synthesis of gangliosides different from that of ganglioside deposition.

Animals↗
PubMed1978

Gangliosides of liver tumors induced by N-2-fluorenylacetamide. I. Ganglioside alterations in liver tumorigenesis and normal development.

Hyperplastic nodules and hepatocellular carcinomas were induced in livers of rats by a low-protein diet containing 0.05% of the carcinogen N-2-fluorenylacetamide. Ganglioside amounts and composition were determined for histologically different hepatocellular carcinomas and compared with those for control livers, hyperplastic nodules, and liver tissue surrounding hepatomas and nodules as well as those for livers of fetal, newborn, 1-week-old, weanling, and adult Sprague-Dawley rats. Ganglioside sialic acid levels were elevated above those of normal adult liver in all liver tissues following the carcinogen treatment regimen. Livers of fetal and newborn rats contained nearly twice the amount of ganglioside sialic acid on a protein or DNA basis as did livers of adult rats. Analyses of individual nodules and hepatomas revealed two populations of tumors in which the levels of ganglioside sialic acid were 2.3 and 3.8 times normal. Ganglioside sialic acid content was at hepatoma levels in small nodules. Individual gangliosides were evenly distributed between products of the monosialoganglioside and disialoganglioside pathways in normal liver with a ratio of [N-acetylneuraminic acid (sialic acid)] (NAN)-galactose (Gal)-N-acetylgalactosamine (GalNAc)-(NAN)-Gal-glucose (Glc)-ceramide (Cer) (GD1a) to Gal-GalNAc-(NAN)2-Gal-Glc-Cer (GD1b) of about one. In contrast, the monosialogangliosides predominated in liver tissues following administration of the carcinogen. Increased levels of specific monosialogangliosides were present in nodules, in liver of carcinogen-treated animals prior to the appearance of tumors, and in the liver tissues surrounding nodules and hepatomas. In single hepatomas, ganglioside patterns correlated with tumorigenicity. A well-differentiated hepatoma had a normal complement of most gangliosides but was deficient in trisialogangliosides. In a poorly diferentiated but well-circumscribed hepatoma, the relative levels of all higher gangliosides were reduced. The monosialoganglioside Gal-GalNAc-(NAN)-Gal-Glc-Cer (GM1) accounted for 80% of the total ganglioside in a poorly circumscribed and poorly differentiated hepatoma. The ganglioside pattern of fetal livers most closely resembled that of a poorly differentiated hepatoma. During the first week post natum, levels of all higher monosialogangliosides and disialogangliosides declined, but the decline was most pronounced for gangliosides GM1 and GD1a. The ratio of GM1 + GD1a to GD1b + NAN-Gal-GalNAc-(NAN)2-Gal-Glc-Cer or (NAN)3-Gal-Glc-Cer (GT), used as an index of the relative predominance of the monoslaloganglioside and disialoganglioside pathways, fell from 2.7 for fetal liver to 0.4 for adult liver. Pools of precursor gangliosides increased during development, transiently for GalNAc-(NAN)-Gal-Glc-Cer and for more than 3 weeks for NAN-Gal-Glc-Cer. When hyperplastic nodules and hepatocellular carcinomas were compared, a reverse pattern was observed. The ratio of GM1 + GD1a to GD1b + GT rose steadily to values of 2.7 and 11...

2-Acetylaminofluorene↗
PubMed1979

Phase behavior of ganglioside-lecithin mixtures. Relation to dispersion of gangliosides in membranes.

Ganglioside GM1 and mixed brain gangliosides were mixed with 1-stearoyl-2-oleoyl lecithin (SOPC) and examined by differential scanning calorimetry as a function of ganglioside content and temperature. Low mole fractions of ganglioside GM1 and of mixed brain gangliosides are shown to be miscible with SOPC in the gel phase up to X = 0.3, with the possible exception of a small region of immiscibility for the mixed brain gangliosides system centered around X = 0.05. Above X = 0.3, the low-temperature phases demix into a (gel) phase of composition X = 0.3 and a (micellar) phase of composition X = 1.0. Above the endothermic phase transition temperature, no phase boundaries are discerned. It is pointed out that phase structures need to be determined in each domain delineated in the phase diagrams, and that cylindrical phases may exist at higher temperatures and intermediate compositions. The effects of addition of wheat germ agglutinin, which binds to ganglioside GM1, on a ganglioside GM1-SOPC mixture (X = 0.5), are described and interpreted in terms of partial demixing of ganglioside and lecithin. Behavior of the ganglioside-SOPC system is discussed with respect to the kinetics of cholera toxin action in lymphocytes, as well as to other physiological roles of gangliosides in membranes.

Calorimetry, Differential Scanning↗
PubMed1978

A new chromatographic approach to the resolution of individual gangliosides. Ganglioside mapping.

1. Anion-exchange column chromatographies on DEAE-Sephadex, DEAE-Sepharose and QAE-Sephadex were tested for fractionation of ganglioside-molecular species. DEAE-Sepharose gave the best resolution, with good separation of mono-, di-, tri- and even tetrasialogangliosides. Even minor gangliosides could be resolved and detected by silica gel thin-layer chromatography of successive fractions of effluent from a DEAE-Sepharose column. In this two-step chromatographic system, the first step of elution from the column depends on differences in anionic charge and the second step of development on a silica gel plate depends on differences in polarity. With this ganglioside-mapping technique, at least 25 unidentified gangliosides were separated from bovine and human brains in addition to the well-known compounds, G7, GM3, GM2, GM1, GM1 (GlycNeu), GD2, GD3, GD1a, GD1a-GAN, GD1a(AcNeu, GlycNeu), GD1b, GT1a, GT1b and GQ. 2. The procedure was used to compare the gangliosides in human (3, 5 and 35 years old), bovine, cat, rat, rabbit, chicken and dog brains. The ganglioside profiles of human, cat, rat, rabbit and dog brains only differed in minor components. However, the gangliosides in chicken brain were unexpectedly complex, at least 30 minor gangliosides, including 15 monosialogangliosides being recognized. Gangliosides containing N-glycolylneuraminic acid (GDIa and GM1 type) were only found in bovine brain. The concentrations of tri- and tetrasialogangliosides in human brain were found to increase during maturation. 3. The long chain bases of each ganglioside fraction, in which the content of sialic acid was confirmed by measuring the ratio of sialic acid to stearic acid, were also analyzed as their aldehydes. The ratios of C-20 to C-18 sphingosine increased in the series from the mono- to tetrasialoganglioside fraction (0.216-1.777) in all animal brains tested.

Adult↗
PubMed1977

Ganglioside content and pattern in human gliomas in culture. Correlation of morphological changes with altered gangliosides.

The ganglioside level and pattern of human gliomas in monolayer cultures were examined. These gliomas revealed morphological variations that correlated with several features of ganglioside analysis. Glioblastoma lines TC 178 and TC 501 that morphologically had changed during extended subculture revealed reduced amounts and a simplified pattern of gangliosides with almost total loss of the characteristic brain complex gangliosides. In contrast, two glioblastoma lines TC 526 and TC 593, as well as the oligodendroglioma line TC 620 showed brain-like gangliosides and the cells in these cultures had maintained their characteristic morphology observed during early subcultures. The possibility that altered ganglioside levels occur in conjunction with morphological changes after propagation in vitro is discussed.

Brain Neoplasms↗
PubMed1978

The biosynthesis of brain gangliosides. Ganglioside-glycosylating activity in rat brain neuronal perikarya fraction.

Rat brain homogenate and the synaptosmal and neuronal perikarya fractions from 17-day-old rats were compared for their activities in sialosylating endogenous gangliosides and transferring N-acetylneuraminic acid and galactose to several glycolipids in vitro. The sialosylation of endogenous gangliosides and the activities of sialosyltransferases acting either on lactosylceramide or haematoside as acceptors, as well as galactosyltransferase acting on Tay-Sachs ganglioside as acceptor, were between 3-and 12-fold higher in the neuronal perikarya fraction than in whole homgenate on a protein or ganglioside basis. The activities found in the synaptosomal fraction were negligible. No evidence was found to indicate that the low activities in this fraction were due to the presence of inhibitors of the transfer activities or to inacessibility of the substrates to their respective enzymes. These findings, and the time course of labelling of gangliosides of the neuronal perikarya and synaptosomes from rats that received an injection of N-[3H]acetylmannosamine, indicate that the main cellular site of glycosylation of neuronal gangliosides is in the neuronal perikarya.

Animals↗
PubMed1979

Isolation and characterization of gangliosides with a new sialosyl linkage and core structures. II. Gangliosides of human erythrocyte membranes.

Eight monosialosylgangliosides, G1 to G8, have been isolated from human erythrocyte membranes and their structures have been determined. Gangliosides G4 and G7 have been characterized by having 2 leads to 6-linked sialic acid to galactose at their termini. Ganglioside G5 was a positional isomer of a brain ganglioside GM1 as to the linkage of sialic acid. Ganglioside G8 was characterized as a branched chain ganglioside similar to a fucoganglioside previously isolated but devoid of fucose, and it showed a strong blood group I activity. Structures of these four new gangliosides are shown below: (formula: see text).

Carbohydrates↗
PubMed1977

[Binding of colchiceine to isolated gangliosides and ganglioside-containing membranes (author's transl)].

The binding of the alkaloid colchicine and its metabolite colchiceine to different membranes and gangliosides has been investigated. In contrast to colchicine, colchiceine binds to erythrocyte ghosts, plasma membranes of rat liver and heart muscle, and synaptosomes of rat brain. The binding properties of isolated gangliosides are analogous to those of the membranes investigated. On a molar basis the binding capacities of the gangliosides GT1, GD1a and GM1 for colchiceine are 7:4:1, respectively. The binding of alkaloid to ganglioside structures is diminished in the presence of EDTA and after pretreatment with neuraminidase, suggesting a specific, Ca2 -dependent interaction of colchiceine with gangliosides. The results are discussed with respect to the different biological activities of colchicine and its metabolite colchiceine.

Animals↗
PubMed1979

Gangliosides of human erythrocytes. A novel ganglioside with a unique N-acetylneuraminosyl-(2 leads to 3)-N-acetylgalactosamine structure.

A novel ganglioside having both N-acetylgalactosamine and N-acetylglucosamine was isolated from human erythrocyte membranes. Its structure was characterized by successive exoglycosidase treatment, methylation analysis, and direct-probe mass spectrometry of permethylated intact and desialylated glycolipid. The core structure of the ganglioside was found to be N-acetylgalactosaminyl paragloboside with sialosyl substitution by 2 leads to 3 linkage at the terminal GalNAc residue: NeuNAc alpha 2 leads to 3 GalNAc beta 1 leads to -3Gal beta 1 leads to 4 GlcNAc beta 1 leads to 3 Gal beta 1 leads to 4Glc leads to Cer. The ganglioside was characterized by the presence of a ceramide with myristic acid as the major component.

Acetylgalactosamine↗
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↗
PubMed1979

Monomer-micelle transition of the ganglioside GM1 and the hydrolysis by Clostridium perfringens neuraminidase.

The action of Clostridium perfringens neuraminidase on the ganglioside Gm1 tritiated in the ceramide moiety was studied. The rates of hydrolysis of the Gm1 ganglioside were determined from radioactivity in the neutral glycolipid product, which was separated from the substrate on DEAE-Sephadex columns. In order to study the physical state of the substrate in the conditions used in the neuraminidase treatment, the critical micelle concentrations of the Gm1 ganglioside were determined using formation of the triiodide anion in aqueous iodine solution as an indicator. The critical micelle concentrations were also obtained by determining the non-sedimenting radioactivity at different concentrations of the labeled ganglioside per total volume used in ultracentrifugation experiments. In addition, the concentrations of the monomeric ganglioside were concluded from the results of the ultra-centrifugation studies. The increase in the reaction rate of the Gm1 hydrolysis as the function of the substrate concentration was leveled off at 25-28 microM ganglioside. The abrupt change at this concentration is interpreted as reflecting the monomer-micelle transition of the ganglioside in the conditions used (50mM sodium acetate buffer, pH 4.6). The critical micelle concentration was 29 microM on the basis of the triiodide test, and ultracentrifugation revealed the critical micelle concentration 28 microM. The reaction velocity of the hydrolysis was decreased immediately above the critical micelle concentration, and became constant at higher concentrations of the ganglioside. A close correlation to these changes in the reaction rate is suggested to exist in the concentrations of the monomeric Gm1 ganglioside. Saturation of the buffer used in the neuraminidase assays with butanol effected a striking change in the plot of reaction rate versus ganglioside concentration. The reaction rate increased up to 100-110 microM Gm1 ganglioside. The shift of the inflexion point in the rate plot from 25-28 microM to 100-110 microM ganglioside concentration is suggested to be due to a respective change in the critical micelle concentration effected by butanol. N-Acetylneuraminyllactosyl ceramide, lactosyl ceramide and asialo-Gm1 ganglioside had an inhibitory effect on the reaction. In contrast, N-acetylneuraminyllactose, lactose and some other free saccharides were not inhibitory. The results demonstrate that factors other than the saccharide structure must be taken into account when substrate specificity of a glycosidase is studied using competition experiments. It is suggested that the inhibition effected by the glycolipids is due to an increase in the micellar state of the Gm1 ganglioside.

Carbohydrates↗
PubMed1977

Synthesis and uptake of gangliosides by choleragen-responsive human fibroblasts.

Human fibroblasts, cultured in medium containing 10% fetal calf serum, responded dramatically to choleragen with an increase in cyclic adenosine monophosphate content to greater than 48 times basal levels. Analysis of these cells for gangliosides indicated that the major ganglioside was N-acetylneuraminylgalactosylglucosylceramide (GM3) with trace amounts (less than or equal to 100 pmol/mg of protein) of other gangliosides including GM1, the putative choleragen receptor. Although the cells contained three glycosyltransferases required for ganglioside synthesis, the N-acetylgalactosaminyltransferase activity necessary for the conversion of GM3 to more complex gangliosides was not detected. When the cells were grown in medium containing [14C]galactose or N-acety[3H]mannosamine, however, all of the gangliosides became labeled, indicating that the cells can synthesize complex gangliosides. Although fetal calf serum contains gangliosides including GM1, [3H]GM1 was taken up poorly from the growth medium and uptake at the rate observed could have accounted for less than 2% of the GM1 content of the cells. When the cells were incubated in chemically defined medium containing [3H]GM1 at the concentrations present in fetal calf serum, rapid uptake of the ganglioside occurred and the total GM1 content of the cells increased threefold in less than 3 h. Thus, although the cells are capable of binding exogenous gangliosides, the gangliosides in fetal calf serum are in a form not readily available to the cells.

Bacterial Toxins↗