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PubMed2001

Gangliosides in rat kidney: composition, distribution, and developmental changes.

Gangliosides in rat kidney were analyzed for their composition, regional distribution, and developmental changes. Renal tissue from 7-week-old rats showed a GM3-dominant pattern with GD3 and several minor ganglioside components including GM4, GM2, GD1a, and an unknown ganglioside (ganglioside X). The tissue also contained c-series gangliosides that included GT3 as the main component with GT2 in a lesser amount. Ganglioside analysis of cortical and medullary regions of renal tissue suggested the restricted localization of some gangliosides. While GM4 and GD3 were enriched in the cortical region, GM2 was distributed mainly in the medullary area. Renal gangliosides showed unique developmental profiles during a period from Embryonic Day 20 (E20) to 7 weeks postnatal. The content of renal gangliosides increased from E20, reached the highest around Postnatal Day 1, and thereafter, decreased rapidly to the adult level. The ratio of N-glycolylneuraminic acid to total sialic acids in gangliosides tended to change in inverse proportion to the amount of total sialic acids. The composition of major gangliosides in renal tissues shifted from GD3-dominant to GM3-dominant patterns with advancing ages. While GM1 was expressed only at early stages of the development, GM4, GM2, and ganglioside X appeared after Postnatal Day 3. The expression of c-series gangliosides was less affected through the period examined. These results suggest that gangliosides may be implicated with development and function of rat kidney.

Animals↗
PubMed2005

Diet-induced changes in membrane gangliosides in rat intestinal mucosa, plasma and brain.

OBJECTIVES: The objective of this study was to determine if dietary gangliosides induce changes in the ganglioside content of intestinal mucosa, plasma and brain and to identify where GM3 and GD3 are localized in the enterocyte membrane. METHODS: Male 18-day-old Sprague-Dawley rats were fed a semipurified diet containing 20% (w/w) fat. The control diet contained triglyceride, reflecting the fat formulation of an existing infant formula. Two experimental diets were formulated by adding sphingomyelin (1% w/w of total fat) or a ganglioside-enriched lipid (0.1% w/w of total fat) to the control diet fat. The ganglioside fraction of ganglioside-enriched lipid diet contained more than 80% GD3. After 2 weeks of feeding, the total and individual ganglioside and cholesterol content was measured in small intestinal mucosa, plasma and brain. RESULTS: The ganglioside-enriched lipid diet significantly increased total gangliosides in the intestinal mucosa, plasma and brain compared with the control diet. The ganglioside-enriched lipid diet significantly increased the level of GD3 (7.5% w/w) in the intestine compared with control (3.2% w/w) while decreasing the level of GM3, the major ganglioside in the intestine. The ratio of cholesterol to ganglioside in the intestinal mucosa, plasma and brain decreased significantly in rats fed the ganglioside-enriched lipid diet compared with controls. Confocal microscopy showed that GM3 is exclusively localized in the apical membrane of the enterocyte whereas GD3 is primarily localized in the basolateral membrane. CONCLUSIONS: : The authors conclude that dietary ganglioside is absorbed in the small intestine and transported to different membrane sites, altering ganglioside levels in the intestinal mucosa, plasma and brain and thus possibly having the potential to change developing enterocyte function (and possibly that of other cell lines).

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↗
PubMed2006

Differential expression of gangliosides in the ovary and uterus of streptozotocin-induced and db/db diabetic mice.

Gangliosides are widely distributed in mammalian cells and play important roles in various functions such as cell differentiation and growth control. In addition, diabetes and obesity cause abnormal development of reproductive processes in a variety of species. However, the mechanisms underlying these effects, and how they are related, are not fully understood. This study examined whether the differential expression of gangliosides is implicated in the abnormal follicular development and uterine architecture of streptozotocin (STZ)-induced and db/db diabetic mice. Based upon the mobility on high-performance thin-layer chromatography, mouse ovary consisted of at least five different ganglioside components, mainly gangliosides GM3, GM1, GD1a and GT1b, and diabetic ovary exhibited a significant reduction in ganglioside expression with apparent changes in the major gangliosides. A prominent immunofluorescence microscopy showed a dramatic loss of ganglioside GD1a expression in the primary, secondary and Graafian follicles of STZ-induced and db/db diabetic mice. A significant decrease in ganglioside GD3 expression was also observed in the ovary of db/db mice. In the uterus of STZ-induced diabetic mice, expression of gangliosides GD1a and GT1b was obviously reduced, but gangliosides GM1, GM2 and GD3 expression was increased. In contrast, the uterus of db/db mice showed a significant increase in gangliosides GM1, GD1a and GD3 expression. Taken together, a complex pattern of ganglioside expression was seen in the ovary and uterus of normoglycemic ICR and db/+ mice, and the correspoding tissues in diabetic mice are characterized by appreciable changes of the major ganglioside expression. These results suggest that alterations in ganglioside expression caused by diabetes mellitus may be implicated in abnormal ovarian development and uterine structure.

Animals↗
PubMed1986

New chemical trends in ganglioside research.

A report is given of recent progress in the methodology for isolation of gangliosides from natural sources, for the preparation of molecular species of gangliosides homogeneous in both the oligosaccharide and ceramide portions of the molecule, for chemical manipulation and derivatization of gangliosides, and for the preparation of gangliosides radiolabelled in different parts of the molecule. Particular emphasis has been given to: high performance liquid chromatographic procedures capable to separate gangliosides on the basis of their oligosaccharide or ceramide moieties and yielding completely homogeneous compounds, that is gangliosides with a single oligosaccharide, a single long chain base and a single fatty acid; two-dimensional thin-layer chromatographic procedures, provided with a fully computerized quantification system, particularly suitable to identifying gangliosides containing alkali-labile linkages, including ganglioside lactones; chemical procedures of high yield for reducing gangliosides at the double bond of long chain base, for selective removal of the fatty acyl moiety and replacement with a novel fatty acid, and for the synthesis of ganglioside lactones; chemical procedures for inserting fluorescent, paramagnetic or photoreactive probes at the fatty acyl part of the ganglioside molecule; procedures for chemical isotopic radiolabelling of gangliosides at the level of sialic acid acetyl group and at the fatty acid moiety. Examples are provided evidencing the significance and potential use of a variety of ganglioside derivatives in the study of ganglioside metabolism and functional implications.

Affinity Labels↗
PubMed1991

Gangliosides in human fetal brain.

The ganglioside concentration and composition were determined in 42 human fetal brains from gestational week 10 to 22, a period that is morphologically characterized by rapid neuroblast proliferation and migration. The ganglioside concentration was constant during this period, approximately 1 mumol of ganglioside sialic acid/g of fresh tissue weight. At gestational week 10 the ganglioside pattern was dominated by gangliosides of the ganglio b series, with the major ganglioside being GT1b, contributing 40% of total ganglioside sialic acid, whereas GD1b and GD3 contributed only 15 and 10%, respectively. The proportion of b series ganglioside decreased to gestational week 22, with the most pronounced relative reduction affecting GD3, but also GT1b and GD1b to a lesser extent. The ganglioside GQ1b increased in content from gestational week 10 and peaked around week 16. The proportion of GD1a increased markedly between gestational week 12 and 14 and slowly between week 14 and 18 and then increased rapidly from week 20. Ganglioside GM1 underwent a similar change. Gangliosides of the lacto series contributed 6-10% of ganglioside sialic acid between gestational week 10 and 15, and thereafter the proportion slowly decreased. 3'-isoLM1 decreased rapidly in content from gestational week 10 (20 nmol/g of fresh weight) to week 22 (less than 0.5 nmol/g of fresh weight), whereas the gangliosides of the neolacto series (3'-LM1 and 3',8'-LD1) showed a slower and less marked decline in level. The biological significance of the ganglioside changes is discussed.

Brain↗
PubMed1997

Specific binding of Haemophilus influenzae to minor gangliosides of human respiratory epithelial cells.

Gangliosides are sialylated glycosphingolipids that serve as receptors for various bacteria. To investigate endogenous gangliosides of human respiratory epithelial cells as potential receptors for Haemophilus influenzae, three strains, including nontypeable H. influenzae (NTHI) 1479, and isogenic fimbriated (f+) and nonfimbriated (f0) H. influenzae type b 770235, were 3H labeled and overlaid on two-dimensional thin-layer chromatography (TLC) plates containing either purified HEp-2 gangliosides or murine brain gangliosides. NTHI 1479 bound exclusively to two distinct minor ganglioside doublets, with mobilities near that of GM1. These minor gangliosides comprised only 14.2 and 9.4% of the total, respectively. NTHI 1479 also bound to a distinct ganglioside of human macrophages whose chromatographic mobilities closely resemble those of one of the NTHI-binding gangliosides of HEp-2 cells. H. influenzae type b 770235 f+ and f0 each bound to a different minor HEp-2 ganglioside doublet, with proportionately weaker affinity for a major ganglioside doublet. Remarkably, none of the three strains bound to any murine brain gangliosides. Moreover, when 80 to 90% of sialic acid residues were enzymatically removed from HEp-2 gangliosides, NTHI 1479 binding was proportionately impaired, compared with untreated controls. Our findings support a role for specific gangliosides of specific cells as receptors for H. influenzae strains. Our findings further demonstrate that individual minor gangliosides possess unique biological properties.

Bacterial Adhesion↗
PubMed1986

Gangliosides modulate sodium transport in cultured toad kidney epithelia.

Cultured A6 epithelial cells from toad kidney form confluent monolayers with tight junctions separating the apical and basolateral membranes. These two membrane domains have distinct compositions and functions. Thus, sodium is actively transported across the epithelia from the apical to basolateral surface via amiloride-inhibitable sodium channels located in the apical membrane. Sodium transport is stimulated by vasopressin, cholera toxin, and 8-bromo-cAMP applied to the basolateral surface where the receptors, adenylate cyclase, and Na+/K+-ATPase are located. In a previous study (Spiegel, S., Blumenthal, R., Fishman, P.H., and Handler, J.S. (1985) Biochim. Biophys. Acta 821, 310-318), we demonstrated that exogenous gangliosides inserted into the apical membrane of A6 epithelia do not redistribute to the basolateral membrane. With the ability to vary selectively the ganglioside composition of the apical membrane, we examined the effects of gangliosides on sodium transport in A6 epithelia. When the apical surface of A6 epithelia were exposed to exogenous gangliosides, sodium transport in response to vasopressin, cholera toxin, and 8-bromo-cAMP was enhanced compared to epithelia not exposed to gangliosides. The effect was observed with bovine brain gangliosides, NeuAc alpha 2----3Gal beta 1----3GalNAc beta 1----4[NeuAc alpha 2----3]Gal beta 1----4Glc beta 1----Cer (GD1a) and Gal beta-1----3GalNAc beta 1----4[NeuAc alpha 2----3]Gal beta 1----4Glc beta 1----Cer (GM1), but not with the less complex ganglioside, Neu-Ac alpha 2----3Gal beta 1----4Glc beta 1----Cer (GM3). We examined A6 cells for endogenous gangliosides and found that, whereas GM3 was a major ganglioside, only trace amounts of GM1 and GD1a were present. Based on cell surface and metabolic labeling studies, these gangliosides were synthesized by the cells and were present on the apical as well as the basolateral surface. Bacterial sialidase, which hydrolyzes more complex gangliosides to GM1, was used to modify the endogenous gangliosides on the apical surface; after sialidase treatment, the epithelia were more responsive to vasopressin, cholera toxin, and 8-bromo-cAMP. Thus, gangliosides may be modulators of sodium channels present in the apical membrane of epithelial cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

The role of gangliosides in the interaction of a growth inhibitor with mouse LM cells.

We have isolated and characterized glycopeptides, derived from mouse and bovine cerebral cortex cells, that inhibit protein synthesis and cell growth of normal but not transformed cells. The inhibitor binds to target cell surfaces, and gangliosides have previously been shown to influence cell sensitivity to the glycopeptides. Preincubation with 3.0 micrograms/ml ganglioside GM1 at 0 degrees C for 3 hr sensitized the mouse L-cell line to the inhibitor, as determined by protein synthesis assays. Preincubation of LM cells with ganglioside GM1 alone did not affect protein synthesis rates. In addition, the gangliosides GD1a and GM3 also sensitized the LM cells to the protein synthesis inhibitory effect of the glycopeptide inhibitor. Binding experiments were performed with 3T3 (sensitive) and LM (insensitive) cells to determine if sensitivity to the glycopeptide inhibitor was reflected in binding of the inhibitor to these cells. Binding of 125I-labeled inhibitor to 3T3 cells was maximal after 60 min at 0 degrees C and saturable at approximately 1 X 10(4) molecules/cell. Furthermore, binding of the inhibitor was dose-dependent, with half-maximal binding at 1.5-2.0 nM and saturation at 8.0-10.0 nM. Scatchard plot analysis indicated that the Kd was about 1 X 10(-9) M and that there are 1 X 10(4) receptors/cell. Binding of the inhibitor to LM cells was maximal after 30 min at 0 degrees C and saturation occurred at 5 X 10(3) molecules/cell. We then examined the possibility that gangliosides are the cellular receptor or co-receptor for the glycopeptide inhibitor. Binding of the inhibitor to ganglioside GM1 was first examined after the ganglioside had been preadsorbed to polystyrene tubes. These experiments indicated that the ganglioside did not bind the inhibitor. Ganglioside-containing liposomes from phosphatidylcholine or LM cell membrane components were also prepared; these artificial membranes did not bind appreciable amounts of the iodinated inhibitor. Competition experiments showed that the gangliosides GM1 and GD1a did not neutralize the protein synthesis inhibitory activity of the glycopeptides, indicating that gangliosides do not directly interact with the glycopeptide inhibitor. In addition, binding of the inhibitor to LM cells preincubated with ganglioside GM1 was studied. Although the binding of the inhibitor to LM cells was one-half that observed for 3T3 cells, incorporation of exogenous gangliosides into LM cells did not result in increased binding of the inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Immunoglobulin G-class mouse monoclonal antibodies to major brain gangliosides.

Mice genetically engineered to lack complex gangliosides are improved hosts for raising antibodies against those gangliosides. We report the generation and characterization of nine immunoglobulin G (IgG)-class monoclonal antibodies (mAbs) raised against the four major brain gangliosides in mammals. These include (designated as ganglioside specificity-IgG subclass) two anti-GM1 mAbs (GM1-1, GM1-2b), three anti-GD1a mAbs (GD1a-1, GD1a-2a, GD1a-2b), one anti-GD1b mAb (GD1b-1), and three anti-GT1b mAbs (GT1b-1, GT1b-2a, GT1b-2b). Each mAb demonstrated high specificity, with little or no cross-reactivity with other major brain gangliosides. Enzyme-linked immunosorbent assay (ELISA) screening against 14 closely related synthetic and purified gangliosides confirmed the high specificity, with no significant cross-reactivity except that of the anti-GD1a mAbs for the closely related minor ganglioside GT1a alpha. All of the mAbs were useful for ELISA, TLC immunooverlay, and immunocytochemistry. Neural cells from wild-type rats and mice were immunostained to differing levels with the anti-ganglioside antibodies, whereas neural cells from mice engineered to lack complex gangliosides (lacking the ganglioside-specific biosynthetic enzyme UDP-GalNAc:GM3/GD3 N-acetylgalactosaminyltransferase) remained unstained, demonstrating that most of the mAbs react only with gangliosides and not with related structures on glycoproteins. These mAbs may provide useful tools for delineation of the expression and function of the major brain gangliosides and for probing the pathology of anti-ganglioside autoimmune diseases.

Animals↗
PubMed1986

The suppressive effect of gangliosides upon IL 2-dependent proliferation as a function of inhibition of IL 2-receptor association.

Gangliosides inhibited the proliferation of mitogen-activated human peripheral blood lymphocytes and the IL 2-dependent growth of murine T cell lines and 5-day-old human PHA lymphoblasts. In the case of the murine cell lines and PHA lymphoblasts, most of the effect of gangliosides could be reversed by the addition of high levels of IL 2. In the case of freshly-stimulated mitogen blasts, however, the ganglioside-induced inhibition could not be reversed by increasing exogenous IL 2 levels. These results indicate that inhibition of proliferation by gangliosides can be divided into IL 2-reversible and IL 2-irreversible mechanisms, the latter of which were predominant during the initial stage of cellular activation. Inclusion of gangliosides in receptor binding assays for radiolabeled IL 2 indicated that the IL 2-reversible mechanism likely involved competition between gangliosides and the cellular receptor for the binding of IL 2. Gangliosides blocked binding of radiolabeled IL 2 to both the high and low affinity forms of the IL 2 receptor, and this effect was most noticeable when the gangliosides and IL 2 were preincubated before addition of the target cells. In contrast, treatment of cells with gangliosides had no effect on the affinity of the cellular IL 2 receptor if the free gangliosides were removed immediately before the binding assay. Gangliosides also blocked the binding of radiolabeled IL 2 to anti-IL 2 antibodies, supporting the notion that their inhibitory effect is mediated via a direct interaction with IL 2. Thus, one major mechanism by which gangliosides block the IL 2-dependent proliferation of activated cells is by the sequestering or inactivation of the IL 2 molecule. This effect is reversible with the addition of excess IL 2, which distinguishes it from other mechanisms of ganglioside-dependent inhibition operating during the cellular activation process.

Antibodies, Monoclonal↗
PubMed2002

Characterization of nuclear gangliosides in rat brain: concentration, composition, and developmental changes.

Nuclear gangliosides were characterized using two distinct fractions of large (N1) and small (N2) nuclear populations from rat brain. The ganglioside concentration of N1 nuclei from adult rat brain was 0.92 microg sialic acid/mg protein, which was about 3.8 times higher than that of N2 nuclei. N1 and N2 nuclear gangliosides showed similar compositional profiles; they contained major gangliosides of GM1, GD1a, GD1b, and GT1b, with GM3 in lesser amounts. c-Series gangliosides such as GT3, GQ1c, and GP1c were also detected in both nuclear preparations. Nuclear localization of gangliosides was confirmed by immunofluorescence with anti-GM1 antibody, cholera toxin B subunit, and c-series ganglioside-specific monoclonal antibody A2B5. Developmental changes of nuclear gangliosides were examined using rats of different ages ranging from embryonic day 14 (E14) to postnatal 7 weeks. The concentration of N1 nuclear gangliosides changed only slightly during development and did not correlate with that of whole-brain gangliosides. The developmental pattern of ganglioside composition of N1 nuclei was also distinguished from that of microsomal membranes; the ganglioside changes in N1 nuclei included reduced expression of di- and polysialogangliosides at E16 and higher proportions of GM3 at early and late stages of the period. These findings suggest that gangliosides in nuclear membranes are developmentally regulated in a distinct manner in brain cells.

Animals↗
PubMed2004

Analysis of gangliosides from carp intestinal mucosa.

The gangliosides of carp intestinal mucosa were isolated and analysed by thin-layer chromatography (TLC), TLC immunostaining test, and TLC/secondary ion mass spectrometry (TLC/SIMS). Four species of gangliosides, designated as G-1, G-2, G-3 and G-4, were separated on TLC. The TLC/SIMS analysis of the G-1 ganglioside of carp intestinal mucosa revealed a series of [M-H](-)ions from m/z 1061 to m/z 1131 representing the molecular mass range of GM4-like ganglioside with NeuAc. G-2, G-3 and G-4 gangliosides were analysed by the TLC immunostaining test. G-2 ganglioside was recognised by the monoclonal antibody specific for ganglioside GM1 (AGM-1 monoclonal antibody). However, G-3 ganglioside migrating on TLC between GM3 and GM1 ganglioside was not recognised by anti-GM3 monoclonal antibody and by AGM-1 monoclonal antibody. Furthermore, G-4 ganglioside with a similar TLC mobility as GD1a ganglioside did not show the reactivity to the anti-GD1a monoclonal antibody. In addition using the AGM-1 monoclonal antibody, the expression of GM1 ganglioside in the carp intestinal tissue was studied. GM1 ganglioside was detected on the epithelial cell surface of carp intestinal mucosa.

Animals↗
PubMed1992

Congregation of gangliosides at the junction between two model membranes.

The diversity and distribution of gangliosides in vertebrate tissue suggests an important role in cellular recognition. Two types of experiments are reported to test the hypothesis that gangliosides can congregate to form an adhesive junction between two membranes. First, to monitor ganglioside distribution and mobility in different regions of two large spherical bilayer membranes, fluorescent derivatives of natural gangliosides were synthesized. Second, the cation carrier nonactin was used as a conductance probe to measure the membrane surface potential, which would be altered if there were a redistribution of the charged gangliosides. These studies were conducted in large spherical artificial membranes made from egg phosphatidylcholine or oleoylpalmitoylphosphatidylcholine with 0-12 mol % bovine brain gangliosides dissolved in n-decane. The fluorescent gangliosides utilized were lucifer yellow adducts to the sialic acids (LY-gangliosides) or a cis-paranaric acid substitution of the N-acyl moiety in the ceramide portion of gangliosides GM1 and GD1a (paranaryl-GM1 and paranaryl-GD1a). The polarized fluorescence from the adhesive junction between two membranes containing LY-gangliosides or either paranarylganglioside was compared to that in nonadhesive regions. For LY-gangliosides, total fluorescence in the junction decreased with time, possibly due to electrostatic repulsion of this highly charged derivative. For paranarylgangliosides, fluorescence in the junction increased 7-fold with time, suggesting congregation of this ganglioside. In both cases, a measure of rotational mobility, fluorescence anisotropy, increased dramatically, about 2-fold, as expected for restricted mobility of adhesive compounds. Independent evidence for congregation of charge-bearing gangliosides was found with the conductance probe nonactin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesiveness↗
PubMed1995

In situ accessibility of murine macrophage gangliosides.

Gangliosides are implicated in cell signal transduction. Prior to investigating this phenomenon in macrophages, the in situ accessibility of gangliosides to macromolecules was assessed for peritoneal macrophages isolated from normal C3H/HeN and endotoxin-hyporesponsive C3H/HeJ mice. C3H/HeJ resident and thioglycolate-elicited macrophage ganglioside patterns are the same as normal strains, and no strain differences in galactose oxidase accessibility for resident or thioglycolate-elicited macrophage gangliosides were found. The only gangliosides accessible to galactose oxidase in resident macrophages are GM1a structures. In thioglycolate-elicited macrophages, an additional ganglioside is accessible. For Escherichia coli-activated macrophages, where ganglioside distribution differs between strains, a difference in galactose oxidase-accessible gangliosides also exists. Escherichia coli-activated C3H/HeN patterns show three triplets absent in C3H/HeJ patterns. There were no differences in ganglioside accessibility to Vibrio cholerae sialidase between the thioglycolate-elicited C3H/HeJ and C3H/HeN macrophages. However, despite differences in sialidase-sensitive ganglioside content between E.coli-activated macrophages of these strains, sialidase accessibility for E.coli-activated macrophages was also similar. Sialidase-susceptible GM3 was cryptic in either strain under all conditions examined. The accessibility of murine macrophage gangliosides to galactose oxidase or sialidase was independent of their sialic acid species and chain length of the ceramide fatty acid. With the exception of GM3, major murine macrophage gangliosides are accessible in situ to macromolecules, especially to exogenous pathogenic bacterial sialidase which can alter macrophage cell surface characteristics. Altered macrophage ganglioside accessibility appears sometimes as a consequence, but not a cause, of C3H/HeJ endotoxin hyporesponsiveness.

Animals↗
PubMed2002

Regulation of growth factor receptors by gangliosides.

Since their discovery in the 1940s, gangliosides have been associated with a number of biological processes, such as growth, differentiation, and toxin uptake. Hypotheses about regulation of these processes by gangliosides are based on indirect observations and lack a clear definition of their mechanisms within the cell. The first insights were provided when a reduction in cell proliferation in the presence of gangliosides was attributed to inhibition of the epidermal growth factor receptor (EGFR). Since that initial finding, most, if not all, growth factor receptors have been described as regulated by gangliosides. In this review, we describe the effects of gangliosides on growth factor receptors, beginning with a list of known effects of gangliosides on growth factor receptors; we then present three models based on fibroblast growth factor (FGFR), platelet-derived growth factor receptor (PDGFR), and EGFR. We focus first on ganglioside modulation of ligand binding; second, we discuss ganglioside regulation of receptor dimerization; and third, we describe a model that implicates gangliosides with receptor activation state and subcellular localization. The methodology used to develop the three models may be extended to all growth factor receptors, bearing in mind that the three models may not be mutually exclusive. We believe that gangliosides do not act independently of many well-established mechanisms of receptor regulation, such as clathrin-coated pit internalization and ubiquitination, but that gangliosides contribute to these functions and to signal transduction pathways. We hypothesize a role for the diverse structures of gangliosides in biology through the organization of the plasma membrane into lipid raft microdomains of unique ganglioside composition, which directly affect the signal duration and membrane localization of the growth factor receptor.

Animals↗
PubMed1995

Gangliosides as a possible receptor on the bovine erythrocytes for Theileria sergenti.

To elucidate whether or not gangliosides on the bovine erythrocytes serve as a receptor for Theileria sergenti merozoites, the reactivities of the T. sergenti piroplasms with gangliosides were studied by the liposome agglutination test. The parasites reacted weakly with I-active ganglioside containing N-acetylneuraminic acid (NeuAc) and strongly with I-active ganglioside containing N-glycolylneuraminic acid (NeuGc). However, none of the other gangliosides expressed on the bovine erythrocytes, such as GM3 (NeuAc), GM3 (NeuGc), sialosylparagloboside (SPG) (NeuAc), SPG (NeuGc), i-active ganglioside (NeuAc), and i-active ganglioside (NeuGc), were recognized. After infection with T. sergenti, furthermore, the content of I-active ganglioside (NeuAc) was less (p < 0.05), and I-active ganglioside (NeuGc) content was much less in the erythrocytes (p < 0.01), though the contents of other NeuAc- and NeuGc-containing gangliosides did not so vary with T. sergenti infection. These results suggest that the parasites recognize the I-active ganglioside as their receptor and bind preferentially to NeuGc-carrying I-active ganglioside rather than to NeuAc-type in the target cell membranes, and that the reduction of the contents of I-active gangliosides (NeuAc and NeuGc) on the erythrocytes was related to T. sergenti infection.

Agglutination Tests↗
PubMed1987

Ganglioside composition of an experimental mouse brain tumor.

The ganglioside composition of an experimental ependymoblastoma was examined in C57BL/6 mice. This tumor was produced by Dr. H. Zimmerman in 1949 from methylcholanthrene implantation in the brain and has been maintained in serial transplants through many generations. The influence of tumor environment on ganglioside composition was determined by studying the tumor growing intracerebrally and s.c. (over the skull and in the flank). The ganglioside composition of this tumor is markedly different from that of adult mouse brain. The total ganglioside sialic acid content (micrograms/100 mg dry weight) of the tumor growing in the cerebrum, s.c. over the skull, and in the flank was 70.4 +/- 3.8 (N = 3), 66.8 (N = 2), and 41.7 +/- 0.7 (N = 3), respectively. These values are about 10-fold lower than the ganglioside content of normal mouse cerebrum. This tumor contained a significant amount of N-glycolyneuraminic acid (NGNA). Histological analysis revealed two basically different cell types. The predominant cell type is densely packed and poorly defined in shape, whereas the minor cell type is less densely packed and fibroblastlike in shape. GM3, which migrates as double bands on thin-layer chromatography, is the predominant ganglioside of this tumor in all three regions of growth. Also present in all regions are gangliosides NGNA-GM3 and GM1. Significant amounts of GD1a, GD1b, GT1b, and GQ1b are present only in the cerebral tumor. These gangliosides therefore represent contaminants from normal brain tissue surrounding the tumor and are not native to the tumor. Ganglioside GD3, however, is a minor component of the tumor. Using a thin-layer chromatography-immunostaining method with anti-GA1 antibody, we found significant amounts of ganglioside with a GA1 oligosaccharide backbone migrating near GD3 and GD2. This tumor is similar to other neural tumors in having elevated amounts of GM3 and reduced amounts of total ganglioside and polysialogangliosides but is unique in having a high content of NGNA-containing gangliosides. The possible origin of the NGNA-containing gangliosides is discussed.

Animals↗