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PubMed1982

Gangliosides in normal and cataractous lenses of several species.

The present study was undertaken to compare the content, composition and distribution of gangliosides in ocular lenses of different species, both normal and cataractous. Gangliosides were extracted from cow, pig, rat and human lens by either the Folch-Suzuki partition procedure or by the modified tetrahydrofuran procedure. Between 20 and 45% more ganglioside was recovered from lenses by the tetrahydrofuran than the Folch-Susuki partition procedure. Cow, pig, rat and human normal lens extracted by the tetrahydrofuran procedure contained, respectively, 24.8, 22.3, 71.2, and 272.5 micrograms of ganglioside sialic acid/g lens (wet wt.). No protein-bound sialic acid was detected in any lens. No significant differences were observed in the content or composition of gangliosides from normal and cataractous human lens and from cataractous rat lens induced by the drug U18666A. Although hematoside (GM3) was the predominant ganglioside in bovine (73%) and pig (68%) lens, small amounts of what appeared to be GM1, GD1a, and GT1 were also detected. GM1 predominated (95%) in rat lens, with the remainder being GM3. This is apparently the highest relative content of GM1 reported in a non-neural tissue. Human lens contains two gangliosides, GM1 (53%) and GM3 (47%). Examination of the distribution of gangliosides between various regions of the bovine lens revealed that the epithelial cell fraction contained an about 10 times higher concentration of total gangliosides than either the lens cortex or nucleus.

Aged↗
PubMed2002

Ganglioside alterations in the central nervous system of rats chronically injected with methylmalonic and propionic acids.

Neurological dysfunction and structural cerebral abnormalities are commonly found in patients with methylmalonic and propionic acidemia. However, the mechanisms underlying the neuropathology of these disorders are poorly understood. We have previously demonstrated that methylmalonic and propionic acids induce a significant reduction of ganglioside N-acetylneuraminic acid in the brain of rats subjected to chronic administration of these metabolites. In the present study, we investigated the in vivo effects of chronic administration of methylmalonic (MMA) and propionic (PA) acids (from the 6th to the 28th day of life) on the distribution and composition of gangliosides in the cerebellum and cerebral cortex of rats. Control rats were treated with the same volumes of saline. It was first verified that MMA and PA treatment did not modify body, cerebellum, or cortical weight, nor the ganglioside concentration in the cerebral cortex of the animals. In contrast, a significant reduction in total ganglioside content in the cerebellum of approximately 20-30% and 50% of control levels occurred in rats injected with MMA and PA, respectively. Moreover, chronic MMA and PA administration did not interfere with the ganglioside pattern in the cerebral cortex, whereas the distribution of individual gangliosides was altered in the cerebellum of MMA- and PA-treated animals. Rats injected with MMA demonstrated a marked decrease in GM1 and GD3, whereas chronic PA treatment provoked a significant reduction of all ganglioside species, with the exception of an increase in GM2. Since gangliosides are closely related to the dendritic surface and other neural membranes, indirectly reflecting synaptogenesis, these ganglioside abnormalities may be associated with the brain damage found in methylmalonic and propionic acidemias.

Animals↗
PubMed2002

Inhibition of human neuroblastoma cell proliferation and EGF receptor phosphorylation by gangliosides GM1, GM3, GD1A and GT1B.

The inhibitory action of gangliosides GT1B, GD1A, GM3 and GM1 on cell proliferation and epidermal growth factor receptor (EGFR) phosphorylation was determined in the N-myc amplified human neuroblastoma cell line NBL-W. The IC50 of each ganglioside was estimated from concentration-response regressions generated by incubating NBL-W cells with incremental concentrations (5-1000 microm) of GT1B, GD1A, GM3 or GM1 for 4 days. Cell proliferation was quantitatively determined by a colourimetric assay using tetrazolium dye and spectrophotometric analysis, and EGFR phosphorylation by densitometry of Western blots. All gangliosides assayed, with the exception of GM1, inhibited NBL-W cell proliferation in a concentration-dependent manner. The IC50s for gangliosides GT1B [molecular weight (MW) 2129], GM3 (MW 1236), and GD1A (MW 1838) were (mean +/- SEM) 117 +/- 26, 255 +/- 29, and 425 +/- 44 m, respectively. In contrast, the IC50 for GM1 (MW 1547) could not be determined. Incubation of NBL-W cells with epidermal growth factor (EGF) concentrations ranging from 0.1 to 1000 ng/ml progressively increased cell proliferation rate, but it plateaued at concentrations above 10 ng/ml. EGFR tyrosine phosphorylation, however, was incrementally stimulated by EGF concentrations from 1 to 100 ng/ml. The suppression of EGF-induced EGFR phosphorylation differed for each ganglioside, and their respective inhibitory potencies were as follows: EGFR phosphorylation [area under curve (+ EGF)/area under curve (- EGF)]: control (no ganglioside added) = 8.2; GM1 = 8.3; GD1A = 6.7; GM3 = 4.87, and GT1B = 4.09. The lower the ratio, the greater the inhibitory activity of the ganglioside. Gangliosides GD1A and GT1B, which have terminal N-acetyl neuraminic acid moieties, as well as one and two N-acetyl neuraminic acid residues linked to the internal galactose, respectively, both inhibited cell proliferation and EGFR phosphorylation. However, GD1A was a more potent suppressor of cell proliferation and GT1B most effective against EGFR phosphorylation. GM3, which only has a terminal N-acetyl neuraminic acid, inhibited cell proliferation and EGFR phosphorylation almost equivalently. These data suggest that gangliosides differ in their potency as inhibitors of NBL-W neuroblastoma cell proliferation and EGFR tyrosine phosphorylation, and that perturbations in the differential expression of membrane glycosphingolipids may play a role in modulating neuroblastoma growth.

Animals↗
PubMed1992

Alteration in keratinocyte ganglioside content in basal cell carcinomas.

We examined the ganglioside content of normal human keratinocytes and basal cell carcinomas (BCC). The total ganglioside content of the epidermis was 0.098 +/- 0.01 microgram lipid-bound sialic acid/mg dry weight. GM3 was the predominant ganglioside of epidermis. GM2 and GD3 were also found in significant amounts. Polysialylated gangliosides were identified in only small amounts. In contrast to all other body locations, breast epidermis showed large amounts of GM1. The total ganglioside content of nodular and sclerosing facial BCC was approximately 3.5 times that of normal facial epidermis. This marked elevation of total ganglioside was not affected by dermal ganglioside contamination, because the total ganglioside content of the dermis was similar to that of the epidermis. The relative percentage of GM2 was significantly decreased, whereas the relative percentage of GM3 was slightly decreased in BCC. 9-O-acetyl-GD3 was present in the BCC, but not in normal epidermis or dermis. 9-O-acetyl-GD3 may be a surface marker for BCC. Furthermore, the alterations in amount and composition of individual gangliosides on neoplastic membranes may lead to novel therapeutic interventions.

Basal Cell Carcinoma↗
PubMed1989

Gangliosides of sea urchin embryos. Their localization and participation in early development.

The influence of antibodies to gangliosides of sea urchin Strongylocentrotus intermedius eggs on early embryos of this species was studied. gamma-Globulins were isolated from rabbit anti-ganglioside serum by micropreparative electrophoresis. These gamma-globulins produced anomalies in the development of embryos permeabilized in Triton X-100. The anomalies were not observed when anti-ganglioside gamma-globulins were added to the incubation medium together with gangliosides or when the permeabilized embryos were incubated with gamma-globulins of normal rabbit serum. Pretreatment of S. intermedius embryos with serotonin, tryptamine or some other indole derivatives led to the disappearance of ganglioside determinants from the cell surface and sharply increased immunofluorescence within the cell. Such pretreatment of embryos increased the amount of cell-associated gangliosides more than threefold as compared to untreated embryos. Serotonin was shown to bind specifically to sea urchin gangliosides immobilized on octyl-Sepharose. These observations suggest that cell-surface gangliosides, after binding drugs, are internalized and that serotonin and its antagonists inhibit the transport of newly synthesized gangliosides to the cell-surface membrane.

Animals↗
PubMed1996

Stimulation of endogenous ganglioside metabolism by neurotrophic growth factors in cultured retinal Müller glia.

Neurotrophic factors such as basic fibroblast and epidermal factor (bFGF and EGF respectively) are known to influence many differentiative processes, but their effects on an important group of glycosylated signalling molecules involved in neural differentiation, the gangliosides, are unknown. To study this possibility, we analyzed the effects of exogenously added bFGF and EGF upon the amount and type of endogenous gangliosides extracted from purified cultures of retinal Müller glial cells. A single addition of 500 pM bFGF or EGF for 48 h to such cultures led to significant increases in total ganglioside levels of 30-40%. Analysis of the distribution of specific ganglioside species within control and growth factor treated cells revealed that the precursor form GM3 formed 50-60% of the total ganglioside pool in all cases, the remainder being composed principally of GD1a (20%) with no detectable tri-sialogangliosides. Growth factor treatment for 48 h led to increases mainly in GM3, whereas longer exposure (96 h) of confluent glial cultures to growth factors additionally stimulated synthesis of GT1b. Furthermore, growth factor-induced ganglioside increases were dose-dependent, reaching maximal stimulation at 500 pM for bFGF. Incorporation of radiolabelled [3H]-glucosamine into glial cultures showed that ganglioside synthesis was stimulated 2-fold by the growth factors. To our knowledge these data constitute the first demonstration of neurotrophic factor stimulation of ganglioside levels in cells of central nervous system origin. Such complex interactions between peptide growth factors and gangliosides, if occurring in vivo, could have important consequences for retinal cell behaviour.

Animals↗
PubMed2005

Gangliosides for acute spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) results in loss of feeling and movement. The consequences can be devastating for the patient and his or her carers. Global estimates of the number of new cases annually range from 15 to 40 per million. Leading causes of acute SCI are road traffic injury, violence, and injuries sustained in sports and other recreational activities. Care for people with SCI has improved, leading to an increase in survival rates. Attempts to improve patients' feeling and movement have involved the use of a wide range of treatments. Gangliosides are compounds that occur naturally in cell membranes. Laboratory studies have suggested they may have protective effects on nerves and even help them to re-grow. Clinical trials have taken place using gangliosides (usually GM1 ganglioside) for a number of neurological conditions. OBJECTIVES: To quantify the evidence for the effectiveness and safety of gangliosides when used to treat acute SCI. SEARCH STRATEGY: We searched the following databases to identify trials for inclusion: CENTRAL, MEDLINE, EMBASE, and the National Research Register. We also searched web-based trials registers, such as Current Controlled Trials. We approached the manufacturers of the most widely used ganglioside and researchers in this field to try to locate any unpublished data. SELECTION CRITERIA: Randomised controlled trials of any ganglioside versus controls, in patients with SCI. Outcome measures specified were: mortality, recovery of motor function, improvement in sensory measures, measures of functional activity, infections and any other adverse events. DATA COLLECTION AND ANALYSIS: Data were extracted from published studies and authors were contacted for further information. All data found was dichotomous and odds ratios (with 95% CIs) were calculated. A fixed-effects model was assumed. MAIN RESULTS: Two studies met the inclusion criteria. There were no deaths in one (n=37). In the other (n=760), there were slightly more deaths in the treatment group than in the control group; odds ratio 1.07 (0.57, 2.00 95%CI) - a result that can be explained by the play of chance. Methodological weaknesses regarding the collection and presentation of data from the two studies made it impossible to reach any conclusions regarding the effect of gangliosides on the other specified outcomes. AUTHORS' CONCLUSIONS: The evidence available does not support the use of ganglioside treatment to reduce the death rate in SCI patients. No evidence has yet emerged that ganglioside treatment improves recovery or quality of life in survivors.

Acute Disease↗
PubMed2001

Ganglioside agglutination immunoassay for rapid detection of autoantibodies in immune-mediated neuropathy.

Elevated levels of serum autoantibodies directed against gangliosides are closely associated with acute and chronic autoimmune neuropathies. An agglutination immunoassay using polystyrene microparticles coated with a total extract of brain gangliosides was used to test patient sera for the presence of anti-ganglioside antibodies. Results were compared with those obtained by ELISA for anti-GM1 and anti-GQ1b ganglioside antibodies. Eight of the twelve sera from patients with multifocal motor neuropathy and seven of the thirteen sera from patients with Guillain-Barré syndrome were positive for the presence of anti-ganglioside antibodies by the ganglioside agglutination immunoassay. The assay compared favorably with the ELISA system in sensitivity and specificity, while requiring a fraction of the time and cost to perform. The new assay can serve as a rapid and effective method for detecting or screening for anti-ganglioside antibodies in patients with acute or chronic immune-mediated neuropathies. It would be particularly useful for detecting antibodies that react with multiple gangliosides, or with minor or as yet uncharacterized gangliosides.

Agglutination↗
PubMed1990

GD3 ganglioside is prevalent in fully differentiated neurons from rat retina.

Adult mammalian retinas contain unusually high amounts of GD3, a ganglioside of the lactosylceramide series. In this respect, they differ from adult avian retina and other regions of the adult avian and mammalian brain, where GD3 is a minor ganglioside and gangliosides of the gangliotetraosylceramide series (GM1, GD1a, GD1b, GT1b) are the predominant ones. We compare here the ganglioside patterns of rat, human, horse, and guinea pig retinas, which are known to differ in the degree of vascularization and astrocytic cell content. All these retinas showed a prevalence of pathway "b" gangliosides over pathway "a" gangliosides but showed no correlation between GD3 content and the degree of vascularization and astrocytic cell content. Immunostaining of rat retina sections showed the presence of GD3 in the inner and outer plexiform layers and also in the ganglion cell and inner nuclear layers. About 60% of the cells dissociated from rat retina showed immuno-colocalization of GD3 and the neuronal marker class III beta tubulin isotype or cholera toxin binding. All morphologically identifiable glial Muller cells coexpress GD3 and gangliotetraosylgangliosides. GD3 was a minor ganglioside among these axonally transported by ganglion cells in rats and guinea pigs, suggesting that it is either not synthesized by ganglion cells or, if so, it is restricted to the cell soma and/or dendritic tree. Our results demonstrate that, unlike neurons from avian retina and other regions of avian and mammalian brain, neurons from mammalian retina not only contain gangliosides of the gangliotetraosylceramide series but also keep a prevalence of gangliosides of the lactosylceramide series (GD3) when they are fully differentiated.

Animals↗
PubMed1983

Absence of ganglioside GM1 in astroglial cells from 21-day old rat brain: immunohistochemical, histochemical, and biochemical studies.

A procedure was developed for the cultivation of cells derived from the cerebral hemispheres of the 21-day old rat. Approximately 98 percent of the cells in a 10 day culture are astrocytes that contain glial fibrillary acidic protein. Analysis of the extracted gangliosides by thin layer chromatography revealed that ganglioside GM1 was absent and that the predominant ganglioside was GM3. Very small amounts of the polysialogangliosides GD1a, GD1b, and GT1b were detected. The concentration of gangliosidic NeuNAc per mg protein in these astrocytes was only 3 percent that observed in the 5 day culture of a mixed cell preparation from newborn rat brain. Immunohistochemical and histochemical studies were performed on the mixed cell population of the minced tissue of 21-day old rat brain prior to cultivation. Astrocytes did not stain for hyaluronectin. These cells also did not provide a positive staining reaction for ganglioside GM1 utilizing the antiganglioside GM1 peroxidase-antiperoxidase procedure and the biotinylated choleragen-avidin-peroxidase procedure. These two histochemical methods for ganglioside GM1 also did not stain astrocytes that had been cultured for 5 days. Oligodendroglial cells, which were also present in the uncultured 21-day-old minced brain tissue, stained positively for ganglioside GM1 and hyaluronectin. Hyaluronectin had previously been shown to be a marker for oligodendroglia. Oligodendroglial cells which were present in the 5 day cultures of 21-day old brain tissue also provided a positive reaction for ganglioside GM1. It is concluded that ganglioside GM1 is absent in astroglia. The presence of small amounts of polysialogangliosides in the "pure" astrocyte preparation is discussed.

Animals↗
PubMed1988

Detection of gangliosides of the GM1b type on high-performance thin-layer chromatography plates by immunostaining after neuraminidase treatment.

A method for the detection of GM1b-type gangliosides in complex mixtures of gangliosides was developed. The procedure involves separation of gangliosides on high-performance thin-layer chromatography plates, fixation of the silica gel, treatment with neuraminidase from Vibrio cholerae in the absence of detergent, and incubation of the plates with GgOse4Cer-specific antibodies. Alkaline phosphatase-conjugated second antibodies are used to visualize bound first antibodies by generating a blue dye from 5-bromo-4-chloro-3-indolylphosphate. The procedure is capable of detecting as little as 30 ng of gangliosides. Gangliosides from murine T lymphocytes and from human brain served as examples. Besides GM1b, GD1 alpha is also detectable by this method, whereas the human brain gangliosides GM1a, GD1a, GD1b, and GT1b are not, because they are neuraminidase resistant. Since terminally sialylated gangliosides such as GM1b were described as virus receptors, and certain other terminally sialylated gangliosides are discussed as tumor markers, this method should be useful to screen gangliosides from different tissues or cell lines for the presence of such components, especially if only small amounts of material are available.

Animals↗
PubMed1994

Modulation of the activity of Clostridium perfringens neuraminidase by the molecular organization of gangliosides in monolayers.

The activity of Clostridium perfringens neuraminidase against gangliosides GM3, GD1a and GM1 was studied in lipid monolayers at the air-buffer solution interface. The enzyme activity assay against pure ganglioside monolayers is based on the markedly different molecular packing areas of the substrate gangliosides and the resulting product glycosphingolipids. This allows to control and monitor the surface pressure and the ganglioside intermolecular organization (cross-sectional packing areas and dipole potentials) in a continuous manner during the catalytic process. It was found that the rate and the extent of the enzymatic reaction depended markedly on the lateral surface pressure. In general, the activity of neuraminidase against GM3 and GD1a was higher at lower surface pressure. This corresponded to larger intermolecular spacings among the ganglioside molecules. Both the activity and the extent of the reaction against GM3 were higher than toward GD1a. GM1 could not be degraded by the enzyme, irrespective of the surface pressure but the enzyme could interact with this ganglioside. A latency period, longer for GM3 than for GD1a, was observed prior to the onset of rapid degradation; this indicates that pre-catalytic steps are occurring at the interface before effective ganglioside degradation takes place. The latency period, the total amount of ganglioside degraded, and the velocity of the reaction varied with the surface pressure in different manners. Our data indicate that the different steps of the catalytic reaction occurring at the surface (i.e., substrate recognition and interfacial adsorption, catalysis, maximum extent of substrate conversion) are independently regulated by the molecular organization of the substrate gangliosides.

Clostridium perfringens↗
PubMed1986

Recent advances in identifying the functions of gangliosides.

The recent development of several new approaches has proven extremely useful in identifying functions for gangliosides, the sialic-acid containing glycosphingolipids. The first is the incorporation of exogenous gangliosides into the plasma membrane of ganglioside-deficient cells. Using this approach, specific gangliosides have been identified as the receptors for certain bacterial toxins and viruses and as important factors in the organization of fibronectin into an extracellular matrix. The second approach has been a ligand blotting technique which allows detection of ganglioside-binding proteins such as toxins and antibodies. Gangliosides are separated by thin-layer chromatography and overlain with the protein of interest. Specific binding of the ligand to gangliosides can then be detected by either direct or indirect methods. The third approach is the use of the B or binding subunit of cholera toxin as a specific probe for endogenous plasma membrane ganglioside function. The ability of the B subunit to alter the growth of cells directly demonstrates a role for gangliosides as biotransducers of signals for the regulation of cell growth.

Animals↗
PubMed1997

Ganglioside expression in lung cancer cell lines.

Gangliosides are complex glycolipid constituents of cell membranes. They are involved in many biological functions including cell-cell recognition, cell-matrix attachment, cell growth and cell differentiation. Analysis of tumor associated gangliosides may aid in the characterisation of tumour cells and their degree of malignant transformation. We have characterised a total of eight lung cancer cell lines (four small cell and four non-small cell lung cancer) with respect to ganglioside and alpha v integrin receptor expression. Ganglioside GD3 was detected using the monoclonal antibody R24. Ganglioside GM1 was detected using the beta-subunit of cholera toxin. Ganglioside 9-O-acetyl GD3 and the alpha v integrin receptor were measured using commercially available monoclonal antibodies. Our results indicate that small cell lung cancer cell lines express significant levels of GD3 and 9-O-acetyl GD3. Ganglioside GM1 and alpha v integrin receptor were not specific to any histological subtype. The expression of ganglioside GM1 and GD3 was independent of cell-cycle phase. We conclude that GD3 and 9-O-acetyl GD3 expression may be additional markers of the Small Cell Lung Cancer phenotype, but their significance is unknown. Therefore a characteristic ganglioside pattern cannot be defined according to histological subtype. alpha v integrin receptor expression is not unique to cells expressing GD3.

Antibodies, Monoclonal↗
PubMed1997

Neutral glycosphingolipids and gangliosides from spleen T lymphoblasts of genetically different inbred mouse strains.

The gangliosides G(M1b), GalNAc-G(M1b) and G(D1alpha) are typical compounds of concanavalin A stimulated splenic T lymphoblasts of CBA/J inbred mice. Their structural characterization has been described in previous studies. The intention of this work was the comparative TLC immunostaining analysis of the glycosphingolipid composition of lectin stimulated splenic T lymphoblasts obtained from six genetically different inbred mouse strains. The strains examined were AKR, BALB/c, C57BL/6, CBA/J, DBA/2 and WHT/Ht, which are commonly used for biochemical and immunological studies. The neutral glycosphingolipid GgOse4Cer, the precursor for G(M1b)-type gangliosides, was expressed by all six strains investigated. AKR, C57BL/6 and DBA/2 showed high and BALB/c, CBA/J and WHT/Ht diminished expression in T lymphoblasts, based on single cell calculation. The gangliosides G(M1b) and GalNAc-G(M1b), elongation products of GgOse4Cer, displayed strain-specific differences in their intensities, which were found to correlate with the intensities of GgOse4Cer expression of the same strains. Concerning sialic acid substitution of gangliosides, G(M1b) and GalNAc-G(M1b) predominantly carry N-acetylneuraminic acid, whereas choleragenoid receptors G(M1a) and Gal-GalNAc-G(M1b), which are also expressed by all six strains, are characterized by dominance of N-glycolylneuraminic acid. Two highly polar gangliosides, designated with X and Y, which have not been previously recognized in murine lymphoid tissue, were detected by positive anti-GalNAc-G(M1b) antibody and choleragenoid binding, respectively. Both gangliosides were restricted to AKR, DBA/2 and C57BL/6 mice. The other three strains BALB/c, CBA/J and WHT/Ht are lacking these structures. In summary, the G(M1b)-type pathway is quite active in all six strains analysed in this study. Strain-specific genetic variations in T lymphoblast gangliosides were observed with the occurrence of gangliosides X and Y. This study and data from other groups strongly indicate for G(M1b)-type gangliosides a functional association with T cell activation and leukocyte mediated reactions.

Animals↗
PubMed2002

Gangliosides inhibit the development from monocytes to dendritic cells.

Dendritic cell (DC) development and function is critical in the initiation phase of any antigen-specific immune response against tumours. Impaired function of DC is one explanation as to how tumours escape immunosurveillance. In the presence of various soluble tumour-related factors DC precursors lose their ability to differentiate into mature DC and to activate T cells. Gangliosides are glycosphingolipids shed by tumours of neuroectodermal origin such as melanoma and neuroblastoma. In this investigation we address the question of whether gangliosides suppress the development and function of monocyte-derived DC in vitro. In the presence of gangliosides, the monocytic DC precursors showed increased adherence, cell spreading and a reduced number of dendrites. The expression of MHC class II molecules, co-stimulatory molecules and the GM-CSF receptor (CD116) on the ganglioside-treated DC was significantly reduced. Furthermore, the function of ganglioside-treated DC was impaired as observed in endocytosis, chemotactic and T cell proliferation assays. In contrast to monocytic DC precursors, mature DC were unaffected even when higher doses of gangliosides were added to the culture. With regard to their carbohydrate structure, five different gangliosides (GM2, GM3, GD2, GD3, GT1b), which are typically shed by melanoma and neuroblastoma, were tested for their ability to suppress DC development and function. Suppression was induced by GM2, but not by the other gangliosides. These data suggest that certain gangliosides impair DC precursors, implying a possible mechanism for tumour escape.

Cell Adhesion↗
PubMedDate not supplied

The effect of storage on the ganglioside content of human platelets.

Gangliosides are glycolipids which contain sialic acid and are found in the membranes of mammalian cells. By analogy with recent studies of other cells, it is possible that gangliosides play a role in the membrane functions and in vivo survival of platelets. In order to determine if ganglioside destruction plays a role in the storage-induced loss of platelet viability and function (storage lesion), the ganglioside content of platelets was measured after 24 and 96 hours of storage. Samples were taken from platelet concentrates that were stored either on a flat-bed shaker (n = 6) or on a circular rotator (n = 6). Total ganglioside content was determined colorimetrically from the total lipid extracts of purified platelet pellets using the Svennerholm resorcinol method. Ganglioside GM3 content was determined by Folch partitioning, high performance thin-layer chromatography, and densitometric scanning. Ganglioside content, measured as microgram of lipid-bound sialic acid per 10(10) platelets, was significantly decreased (p less than 0.005) between 24 and 96 hours of storage, whether measured as total or GM3 ganglioside. The mean values +/- SEM at 24 and 96 hours of storage were 9.4 +/- 0.6 and 6.7 +/- 0.6, respectively (n = 12 for each). These data indicate that storage causes irreversible loss of membrane ganglioside, which may be detrimental to the function and in vivo survival of platelets.

Blood Platelets↗
PubMed2004

The plasma membrane-associated sialidase MmNEU3 modifies the ganglioside pattern of adjacent cells supporting its involvement in cell-to-cell interactions.

We describe herein the enzyme behavior of MmNEU3, the plasma membrane-associated sialidase from mouse (Mus musculus). MmNEU3 is localized at the plasma membrane as demonstrated directly by confocal microscopy analysis. In addition, administration of the radiolabeled ganglioside GD1a to MmNEU3-transfected cells, under conditions that prevent lysosomal activity, led to its hydrolysis into ganglioside GM1, further indicating the plasma membrane topology of MmNEU3. Metabolic labeling with [1-(3)H]sphingosine allowed the characterization of the ganglioside patterns of COS-7 cells. MmNEU3 expression in COS-7 cells led to an extensive modification of the cell ganglioside pattern, i.e. GM3 and GD1a content was decreased to about one-third compared with mock-transfected cells. At the same time, a 35% increase in ganglioside GM1 content was observed. Mixed culture of MmNEU3-transfected cells with [1-(3)H]sphingosine-labeled cells demonstrates that the enzyme present at the cell surface is able to recognize gangliosides exposed on the membrane of nearby cells. Under these experimental conditions, the extent of ganglioside pattern changes was a function of MmNEU3 transient expression. Overall, the variations in GM3, GD1a, and GM1 content were very similar to those observed in the case of [1-(3)H]sphingosine-labeled MmNEU3-transfected cells, indicating that the enzyme mainly exerted its activity toward ganglioside substrates present at the surface of neighboring cells. These results indicate that the plasma membrane-associated sialidase MmNEU3 is able to hydrolyze ganglioside substrates in intact living cells at a neutral pH, mainly through cell-to-cell interactions.

Animals↗