Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GANGLIOSIDES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,315 records · Page 73Linked to original sources
PubMed1998

Structural transitions associated with the interaction of Alzheimer beta-amyloid peptides with gangliosides.

Alzheimer's disease is characterized pathologically by the presence of neurofibrillary tangles and amyloid plaques. The principal component of the plaque is the beta-amyloid peptide (Abeta), a 39-43-residue peptide. The conformational change required for the conversion of soluble peptide into amyloid fibrils is modulated by pH, Abeta concentration, addition of kinetic and thermodynamic enhancers, and alterations in the primary sequence of Abeta. We report here the ability of gangliosides to induce an alpha-helical structure in Abeta and thereby diminish fibrillogenesis. Circular dichroism and a fluorescence dye release assay data indicate that gangliosides interact with and induce alpha-helix formation in Abeta. We find that the sialic acid moiety of gangliosides is necessary for the induction of alpha-helical structure. Differences in the amount and the position of the sialic acid on the carbohydrate backbone also affect the conformational switch. The Abeta-ganglioside interaction at pH 7.0, monitored by CD, is stable over time and resistant to high concentrations of NaCl. The induction of alpha-helical structure is greater with Abeta1-40 than Abeta1-42. The ability of gangliosides to sequester Abeta from fibril formation was also evaluated by electron microscopy.

Alzheimer Disease↗
PubMed1999

Enhanced binding of the neural siglecs, myelin-associated glycoprotein and Schwann cell myelin protein, to Chol-1 (alpha-series) gangliosides and novel sulfated Chol-1 analogs.

Extended glycoconjugate binding specificities of three sialic acid-dependent immunoglobulin-like family member lectins (siglecs), myelin-associated glycoprotein (MAG), Schwann cell myelin protein (SMP), and sialoadhesin, were compared by measuring siglec-mediated cell adhesion to immobilized gangliosides. Synthetic gangliosides bearing the alpha-series determinant (NeuAc alpha2,6-linked to GalNAc on a gangliotetraose core) were tested, including GD1alpha (IV(3)NeuAc, III(6)NeuAc-Gg(4)OseCer), GD1alpha with modified sialic acid residues at the III(6)-position, and the "Chol-1" gangliosides GT1aalpha (IV(3)NeuAc, III(6)NeuAc, II(3)NeuAc-Gg(4)OseCer) and GQ1balpha (IV(3)NeuAc, III(6)NeuAc, II(3)(NeuAc)(2)-Gg(4)OseCer). The alpha-series gangliosides displayed enhanced potency for MAG- and SMP-mediated cell adhesion (GQ1balpha > GT1aalpha, GD1alpha > GT1b, GD1a >> GM1 (nonbinding)), whereas sialoadhesin-mediated adhesion was comparable with alpha-series and non-alpha-series gangliosides. GD1alpha derivatives with modified sialic acids (7-, 8-, or 9-deoxy) or sulfate (instead of sialic acid) at the III(6)-position supported adhesion comparable with that of GD1alpha. Notably, a novel GT1aalpha analog with sulfates at two internal sites of sialylation (NeuAcalpha2,3Galbeta1,4GalNAc-6-sulfatebeta1, 4Gal3-sulfatebeta1,4Glcbeta1,1'ceramide) was the most potent siglec-binding structure tested to date (10-fold more potent than GT1aalpha in supporting MAG and SMP binding). Together with prior studies, these data indicate that MAG and SMP display an extended structural specificity with a requirement for a terminal alpha2, 3-linked NeuAc and great enhancement by nearby precisely spaced anionic charges.

Animals↗
PubMed1999

Molecular cloning and characterization of a plasma membrane-associated sialidase specific for gangliosides.

Gangliosides are plasma membrane components thought to play important roles in cell surface interactions, cell differentiation, and transmembrane signaling. A mammalian sialidase located in plasma membranes is unique in specifically hydrolyzing gangliosides, suggesting crucial roles in regulation of cell surface functions. Here we describe the cloning and expression of a cDNA for the ganglioside sialidase, isolated from a bovine brain cDNA library based on the amino acid sequence of the purified enzyme from bovine brain. This cDNA encodes a 428-amino acid protein containing a putative transmembrane domain and the three Asp boxes characteristic of sialidases and sharing 19-38% sequence identity with other sialidases. Northern blot and polymerase chain reaction analyses revealed a general distribution of the gene in mammalian species, including man, and the mouse. In COS-7 cells transiently expressing the sialidase, the activity was found to be 40-fold that of the control level with ganglioside substrates in the presence of Triton X-100, and the hydrolysis was almost specific to gangliosides other than GM1 and GM2, both alpha2-->3 and alpha2-->8 sialyl linkages being susceptible. The major subcellular localization of the expressed sialidase was assessed to be plasma membrane by Percoll density gradient centrifugation of cell homogenates and by immunofluorescence staining of the transfected COS-7 cells. Analysis of the membrane topology by protease protection assay suggested that this sialidase has a type I membrane orientation with its amino terminus facing to the extracytoplasmic side and lacking a signal sequence.

Amino Acid Sequence↗
PubMed2000

Carbohydrate-carbohydrate binding of ganglioside to integrin alpha(5) modulates alpha(5)beta(1) function.

Gangliosides GT1b and GD3, components of keratinocyte membranes, inhibit keratinocyte adhesion to fibronectin. Although ganglioside sialylation is known to be important, the mechanism of inhibition is unknown. Using purified insect recombinant alpha(5) and beta(1) proteins and alpha(5)beta(1) integrin from lysed keratinocyte-derived SCC12 cells, we have shown that GT1b and GD3 inhibit the binding of alpha(5)beta(1) to fibronectin. Co-immunoprecipitation of GT1b and alpha(5)beta(1) from SCC12 cells and direct binding of GT1b and GD3 to affinity-purified alpha(5)beta(1) from SCC12 cells and insect recombinant alpha(5)beta(1), particularly the alpha(5) subunit, further suggest interaction between ganglioside and alpha(5)beta(1). The carbohydrate moieties of integrin appear to be critical since gangliosides are unable to bind deglycosylated forms of alpha(5)beta(1) from SCC12 and insect cells or poorly glycosylated recombinant alpha(5)beta(1) from Escherichia coli cells. The GT1b-alpha(5)beta(1) interaction is inhibited by concanavalin A, suggesting that GT1b binds to mannose structures in alpha(5)beta(1). The preferential binding of GT1b to high mannose rather than reduced mannose ovalbumin further implicates the binding of GT1b to mannose structures. These data provide evidence that highly sialylated gangliosides regulate alpha(5)beta(1)-mediated adhesion of epithelial cells to fibronectin through carbohydrate-carbohydrate interactions between GT1b and the alpha(5) subunit of alpha(5)beta(1) integrin.

Cell Adhesion↗
PubMed2001

Rapid fractionation of bovine transferrin using immobilized gangliosides.

Bovine transferrin (BTF) was fractionated from bovine whey using ganglioside affinity chromatography. After loading the immobilized matrix with a 2% whey solution, the matrix was washed with sodium acetate buffer at pH 4 containing 1 M NaCl before elution of BTF with sodium phosphate buffers at pH 7. Concanavalin-A affinity and ion exchange chromatography were used for further purification. The ganglioside column showed a 74.2% BTF recovery from whey and BTF was enriched to 61% purity with ion exchange chromatography. Bovine transferrin was identified by SDS-PAGE and western analysis. The Concanavalin-A affinity and ion exchange chromatography steps enriched BTF in the samples and removed other whey proteins from ganglioside purified fractions. These results indicate that immobilized ganglioside can be used to fractionate BTF from bovine whey. Our novel ganglioside affinity chromatography is rapid and efficient for the fractionation of BTF from whey.

Animals↗
PubMed1986

Variants of BALB/c 3T3 cells lacking complex gangliosides retain a fibronectin matrix and spread normally on fibronectin-coated substrates.

Evidence has accumulated that di- and trisialogangliosides are involved in the interaction of cells with fibronectin. We have therefore tested the ability of variants of BALB/c 3T3 deficient in such gangliosides to organize a fibronectin matrix and to spread on fibronectin-coated substrates. Whereas BALB/c 3T3 cells contained gangliosides GM3, GM1, and GD1a, direct chemical analysis showed that five out of six variants isolated contained no detectable GD1a. By the overlaying of thin layer chromatograms of cellular gangliosides with 125I-cholera toxin, these variants were also found to lack ganglioside GM1. In contrast, the sialogalactoprotein profile of these cells, analyzed using an 125I-ricin/SDS polyacrylamide gel overlay technique, was similar to that of the parent cell line. All variants organized an extensive fibronectin matrix comparable to that of BALB/c 3T3, as shown using either immunofluorescence or lactoperoxidase-catalyzed iodination. The variants could also spread on fibronectin-coated substrates and adopt a morphology similar to that of BALB/c 3T3 cells, with little or no difference in the concentration of fibronectin required for 50% cell spreading. Cell spreading of the variants was accompanied by the formation of focal contacts and microfilament bundles, in a manner closely resembling that seen with BALB/c 3T3 cells. Treatment of BALB/c 3T3 cells with neuraminidase, which converts much of the cellular GD1a to GM1, did not affect cell spreading on fibronectin. The results clearly demonstrate that complex gangliosides are not essential for retention of a fibronectin matrix or for spreading on fibronectin-coated substrates.

Actin Cytoskeleton↗
PubMed1982

GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody.

Mouse monoclonal antibody AbR24 has a high degree of specificity for human melanoma cells when tested on viable cultured cells using the protein A mixed hemagglutinin serological assay. The antigen detected by this antibody has been isolated from melanoma cells and shown to be GD3 ganglioside by compositional and partial structural analysis and by comparison with authentic GD3 in thin layer chromatography (TLC). AbR24 reacts with authentic GD3, but not with any other ganglioside tested. Using TLC and reactivity with AbR24, a wide range of cells and tissues was examined for the presence of GD3. A new serological assay, termed glycolipid-mediated immune adherence, was devised for assaying the reactivity of AbR24 with gangliosides. Melanomas (cultured cells or tumor tissue) were shown to have GD3 and GM3 as major gangliosides. Other cells and tissues examined also contained GD3, but usually only in low amounts. Melanomas (and MOLT-4, a T cell line) were characterized by a simplified ganglioside profile with GD3 and GM3 as major components. The apparent discrepancy between the ubiquitous presence of GD3 and the serological specificity of AbR24 for melanoma cells can be explained in terms of localization and concentration of GD3 in different cells.

Animals↗
PubMed1997

Molecular mimicry between gangliosides and lipopolysaccharides of Campylobacter jejuni isolated from patients with Guillain-Barré syndrome and Miller Fisher syndrome.

Some patients developed Guillain-Barré syndrome (GBS) after being given bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Miller Fisher syndrome (MFS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. The existence of molecular mimicry between GM1 and lipopolysaccharide of C. jejuni isolated from a GBS patient and that between GQ1b and C. jejuni lipopolysaccharides from patients with MFS are shown herein. The molecular mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies and the development of GBS and MFS.

Antibodies, Bacterial↗
PubMed1982

Inhibition of beta-interferon augmentation of murine natural killer cytotoxicity by gangliosides.

Interferons cause augmentation of natural killer (NK) cell activity, which might be a major reason for their antitumor effect. Antiviral and antigrowth effects of mouse beta interferon are inhibited by mono-, di-, and trisialogangliosides commonly found in brain extracts, but also in membranes of many other cells. Results presented in this report show that preincubation of mouse beta interferon with a brain ganglioside mixture or its isolated major components Gm1, Gd1a, Gd1b, and Gt1b (see Aberrations) prior to addition to effector spleen cells, inhibits NK-cell enhancement due to interferon in a dose-dependent manner. When spleen cells are treated with individual gangliosides alone, spontaneous NK cell activity is not affected. Pretreatment of effector cells with gangliosides prior to addition of interferon does not inhibit subsequent augmentation of NK cell activity by beta interferon. Also, target susceptibility remains unaltered in the presence of gangliosides. Thus the inhibitory effect of gangliosides appears to involve competition for interaction of beta interferon with the NK cells.

Animals↗
PubMed1995

Differential distribution of gangliosides in adult rat ovary during the oestrous cycle.

Gangliosides are ubiquitous membrane components in mammalian cells and are suggested to play important roles in various cell functions, such as cell-cell recognition, differentiation and transmembrane signalling. Rat ovary contained GM3, GD3 and GD1a as major gangliosides, and GM1 as a minor one. In order to study their distribution in the rat ovary and its possible changes during the oestrous cycle, frozen sections were stained with specific monoclonal antibodies against 11 ganglio-series gangliosides including those mentioned above. GM3, GM1 and GD1a were expressed in a spatio-temporally different manner during the oestrous cycle, but GD3 and other gangliosides were not immunohistochemically detected. In primary and secondary follicles, GM3, GM1 and GD1a were expressed in theca cells, but not in granulosa cells. The oocyte in primary, but not secondary, follicles was positive to the anti-GD1a antibody. In Graafian follicles, GM1 and GD1a were similarly expressed as in secondary follicles, however, the expression of GM3 spread gradually from theca cells to granulosa cells. In early Graafian follicles, only GM3 was expressed to a detectable extent from the outer part of the granulosa layer to the inner part. Shortly before ovulation, all granulosa cells and cumulus cells became positive to anti-GM3 antibody. After ovulation, differential distribution of GM3, GM1 and GD1a was also observed in luteal cells. GD1a was localized in thread-like structures, while GM3 was distributed throughout the cytoplasm, but not in the nucleus. GM1 was localized only in the plasma membrane and/or its close vicinity. Other ganglio-series gangliosides, including GD3, were not detected to an appreciable extent in the ovaries by immunohistochemistry.

Animals↗
PubMed1998

Specificity of the N1 and N2 sialidase subtypes of human influenza A virus for natural and synthetic gangliosides.

Sialyl-linkage specificity of sialidases of the human influenza A virus strains, A/Aichi/2/68 (H3N2) and A/PR/8/34 (H1N1) were studied using natural and synthetic gangliosides. The sialidase of the A/Aichi/2/68 strain hydrolyzed the terminal Neu5Acalpha2-3Gal sequence but not the Neu5Acalpha2-3 linkage on the inner Gal of GM1a, which is a ganglioside that has the gangliotetraose chain (Galbeta1-3GalNAcbeta1-4-(Neu5Acalpha2-3)Galbeta1++ +-4Glcbeta1-Cer). The sialidase hydrolyzed the Neu5Ac on the inner Gal of GM2, which had a shorter gangliotriose chain. GM4, which had the shortest chain (Neu5Acalpha2-3Galbeta1-Cer) of the gangliosides, had a lower substrate specificity. The N1 and N2 sialidase subtypes of the human influenza A virus had no significant variation in their substrate specificity for the gangliosides. Analysis of 11 synthetic gangliosides, which contained various ceramide or sialic acid moieties, demonstrated that A/Aichi/2/68 (H3N2) sialidase recognized the ceramide and sialic acid moiety and the length and structure of the sialyl sugar chain.

Carbohydrate Sequence↗
PubMed1999

Prevention of the death of the rat axotomized hypoglossal nerve and promotion of its regeneration by bovine brain gangliosides.

We have examined the time course of the neuronal death and regeneration of rat axotomized hypoglossal nerve with various conditions of the nerve resection, and established a useful system to measure neurotrophic activities of bioactive substances. In this system, neuronal death can be evaluated by counting surviving neurons in the nucleus of hypoglossal neuron at the brain stem, and the degree of the regeneration can be measured by counting horseradish peroxidase-positive cells at the same region after injection of horseradish peroxidase into tongue. Using this system, the effects of brain gangliosides on rat hypoglossal nerve regeneration following 5 mm transection were examined. The addition of a ganglioside mixture from bovine brain as well as the autograft strongly prevented the death of neurons and promoted the regeneration of the lesioned nerve at 10 weeks after the operation. Further analyses on the dose effects and injection sites of gangliosides were performed. Although the mechanisms of the neurotrophic effects of the gangliosides are unknown, the therapeutic application of gangliosides for neuronal degeneration is a promising approach.

Animals↗
PubMed1993

Gangliosides can activate human alternative complement pathway.

The alternative complement pathway (ACP) in vertebrates is known to be important in inflammatory reactions, and to be activated by foreign substances such as bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic activators have been identified except complement receptor type 2. From the point of the structural similarity of LPS to ganglioside, we have investigated gangliosides which are abundantly present in animal cells for their activity on the human ACP. All of seven gangliosides tested were found to activate this pathway in a manner depending on the number of sialic acids and neutral sugars contained in the molecules. A dose-response study suggested a correlation of the threshold in ganglioside concentration with its critical micelle concentration. Gangliosides may thus serve as an intrinsic activator for ACP in animals, thereby leading to inflammation. The possibility of the participation of sialidase in complement activation is also discussed.

Complement Pathway, Alternative↗
PubMed1987

Isolation and characterization of major gangliosides from frog liver.

Four major gangliosides isolated from frog liver were characterized by compositional analysis involving GLC and GC-MS, methylation analysis, chromium trioxide oxidation, and enzymatic hydrolysis. The results revealed that the most major ganglioside in the tissue was GM4 containing N-acetylneuraminic acid and the others were GM4 containing N-glycolylneuraminic acid, GD1a, and a fucosyl ganglioside which was tentatively assigned to be alpha-galactosyl alpha-fucosyl GM1. This is the first report describing the presence of GM4 containing N-glycolylneuraminic acid. The fatty acids in both GM4 were mainly alpha-hydroxylated, and those in the fucosyl ganglioside were exclusively nonhydroxy fatty acids. The GD1a contained both nonhydroxy and alpha-hydroxy fatty acids in a ratio of about 3:2. The predominant species were 22:0, 23:0, 24:0, and 24:1 in both species of the fatty acids. The long-chain bases of these four gangliosides consisted of C18-sphingosine and C18-phytosphingosine together with significant amounts of C16 to C19 dihydroxy and trihydroxy bases with iso and anteiso structures.

Animals↗
PubMed1990

Gangliosides from the eggs of the sea urchin, Anthocidaris crassispina.

NeuGc alpha 2-6Glc beta 1-1Cer (M5 ganglioside) and HSO3-8NeuGc alpha 2-6Glc beta 1-1Cer (T1 ganglioside) were purified by column chromatographies with DEAE-Sephadex A-25 and silicic acid from the eggs of the sea urchin, Anthocidaris crassispina. Their chemical structures were determined by gas-liquid chromatography, methylation analysis, enzymatic hydrolysis, negative-ion fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy. Long-chain base compositions of both gangliosides were almost identical: all the long-chain bases were phytosphingosines, and C18-phytosphingosine accounted for more than 95% of them. Fatty acid compositions were also very similar: the main fatty acids were 22:1, 23:1, 24:1, and their 2-hydroxylated forms, and the 2-hydroxy fatty acids amounted to 65.3 and 74.3% of the fatty acids in M5 and T1 gangliosides, respectively. Proton nuclear magnetic resonance spectroscopic study revealed a downfield-shifted H8 proton signal of NeuGc residue in T1 ganglioside, in agreement with the presence of sulfate ester at the C8 position.

Animals↗
PubMed1990

Immunocytochemical study of the distribution of a ganglioside in sea urchin eggs.

An antibody against M5 ganglioside (NeuGc alpha 2-6Glc beta 1-1Cer), the dominant ganglioside in the eggs of the sea urchin, Anthocidaris crassispina, was purified by affinity chromatography from rabbit antiserum against crude ganglioside of the eggs. The specificity of the antibody was verified by enzyme-linked immunosorbent assay and TLC immunostaining. M5 ganglioside was also the major one in the eggs of another sea urchin, Hemicentrotus pulcherrimus, as judged from TLC analyses including immunostaining. Cryostat-sections of H. pulcherrimus eggs were examined to determine the distribution of M5 ganglioside by indirect immunofluorescence microscopy with the antibody. Before fertilization, the egg cortex was highly stained, while the other part of cytoplasm was uniformly but much more weakly stained. After fertilization, the staining rapidly decreased in the cortex and was restricted to a very thin peripheral layer and to cytoplasmic patches. The immunoreactivity was also observed in the esophagus and the somatic cells of the testis, but the spermatozoa were never stained with the antibody.

Animals↗
PubMed1981

A trisialosyl ganglioside GT3 of hog kidney. Structure and biosynthesis in vitro.

A trisialosyl ganglioside was isolated from hog kidney cortex and purified with a yield of 6.8 nmol/g tissue or 13 mol % of total gangliosides. The homogeneous ganglioside was subjected to graded neuraminidase treatment, mild acid hydrolysis, periodate oxidation-borohydride reduction, permethylation analysis and chromium trioxide oxidation. The results suggested that the structure of this ganglioside is NeuAc alpha 2-8NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1Cer (GT3). On the addition of exogenous disialosyl ganglioside GD3 and radioactive CMP-NeuAc, a GT3 synthesis activity was demonstrated in a crude membrane fraction of hog kidney. The activity was greatest in the presence of detergents and had a pH optimum of 6.4. Apparent Km values for CMP-NeuAc and GD3 were about 0. 6 and 0.1 mM, respectively. The reaction produce was assigned as GT3 by chromatographic separation, carbohydrate analysis and periodate oxidation followed by borohydride reduction.

Animals↗
PubMed1982

Bromodeoxyuridine-induced molecular species conversion of sialic acids of gangliosides and the alteration of cellular phenotypic expression in B16 mouse melanoma cells.

Gangliosides of B16 mouse melanoma cells were characterized and the effects of 5-bromodeoxyuridine (BrdU) on gangliosides were examined in relation to the alteration of cellular phenotypic expression. In melanotic cells, gangliosides were shown to be composed of both hematosides containing N-acetylneuraminic acid (NeuAc-hematoside) and N-glycolylneuraminic acid (NeuGc-hematoside) as determined by thin-layer chromatography, gas chromatography-mass spectrometry and the use of anti-NeuGc-hematoside antiserum. Gangliosides other than hematosides were not detectable under the conditions of thin-layer chromatography employed. BrdU treatment of the melanotic cells induced about a two-fold increase in the ratio of NeuGc-hematosides to the total hematosides without any significant change in the cellular ganglioside content. The treatment concomitantly induced a change in cellular morphology, an increase in cell-to-substrate adhesiveness, and the suppression of tyrosinase activity. Amelanotic cells, which showed cellular phenotypes similar to those of BrdU-treated melanotic cells, were demonstrated to have over twice as much NeuGc-hematosides as compared with the melanotic cells. These results indicate a possible relationship in melanoma cells between the molecular species conversion of sialic acids of hematosides and the alteration of cellular phenotypic expression by BrdU treatment or spontaneous amelanization.

Animals↗