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 955 records · Page 53Linked to original sources
PubMed1991

Multiple-dose pharmacokinetics of ganglioside GM1 after intravenous and intramuscular administration to healthy volunteers.

Ganglioside GM1 multiple-dose pharmacokinetics were investigated in five healthy male volunteers. Doses of 100 mg were administered either intravenously or intramuscularly for 21 days, and the washout was followed-up for a further 21 days. The highly specific binding of the beta-subunit of cholera toxin was used to quantify ganglioside GM1 levels in plasma, urine, and feces. This dose regime increased the ganglioside GM1 steady-state plasma levels two to three orders of magnitude above the endogenous levels of 0.132 mg/L (coefficient of variation, 8.9%). Large and variable amounts of ganglioside GM1 were found in feces before and during treatment without relation to the dosage. No ganglioside GM1 could be detected in urine at any time. Plasma kinetics were linear with a biexponential disposition. Exogenously administered ganglioside GM1 was confined mainly to the blood volume as indicated by a steady-state volume of distribution of 6.98 +/- 3.57 L and appears to be excreted mainly in the form of metabolites. The total clearance was very slow at 1.61 +/- 0.37 ml/min. Absorption after intramuscular administration was slow (time to reach maximum concentration greater than 12 hours) and yielded steady-state concentrations somewhat lower compared with the intravenous infusion.

Adult↗
PubMed2006

Gangliosides as apoptotic signals in ER stress response.

Renewed attention has been given lately to gangliosides and to their function as intracellular messengers of the adaptive responses to stress. Gangliosides are vital components of cell membranes; therefore, deleterious consequences can result from changes in their chemical composition and concentration, that is, membrane dynamics and structure can be altered as can the behavior of other membrane proteins. The importance of gangliosides in human health is evident in neurodegenerative diseases associated with defects in their degradation. As key modulators of intracellular calcium flux, gangliosides are involved in cellular processes downstream of calcium signaling. In this review, we focus on the effect of ganglioside accumulation on the endoplasmic reticulum calcium homeostasis and on the integrity of the mitochondrial membranes. We discuss how these events elicit an apoptotic program that ultimately leads to cell death. Owing to interorganelle crosstalk, these events are not necessarily self-contained, and gangliosides may serve as the common factor.

Animals↗
PubMed2006

Gangliosides of myelosupportive stroma cells are transferred to myeloid progenitors and are required for their survival and proliferation.

In previous studies, we have shown that the myelopoiesis dependent upon myelosupportive stroma required production of growth factors and heparan-sulphate proteoglycans, as well as generation of a negatively charged sialidase-sensitive intercellular environment between the stroma and the myeloid progenitors. In the present study, we have investigated the production, distribution and role of gangliosides in an experimental model of in vitro myelopoiesis dependent upon AFT-024 murine liver-derived stroma. We used the FDC-P1 cell line, which is dependent upon GM-CSF (granulocyte/macrophage colony-stimulating factor) for both survival and proliferation, as a reporter system to monitor bioavailability and local activity of GM-CSF. G(M3) was the major ganglioside produced by stroma, but not by myeloid cells, and it was required for optimal stroma myelosupportive function. It was released into the supernatant and selectively incorporated into the myeloid progenitor cells, where it segregated into rafts in which it co-localized with the GM-CSF-receptor alpha chain. This ganglioside was also metabolized further by myeloid cells into gangliosides of the a and b series, similar to endogenous G(M3). In these cells, G(M1) was the major ganglioside and it was segregated at the interface by stroma and myeloid cells, partially co-localizing with the GM-CSF-receptor alpha chain. We conclude that myelosupportive stroma cells produce and secrete the required growth factors, the cofactors such as heparan sulphate proteoglycans, and also supply gangliosides that are transferred from stroma to target cells, generating on the latter ones specific membrane domains with molecular complexes that include growth factor receptors.

Animals↗
PubMed1985

Gangliosides and sialosylglycoproteins in coated vesicles from bovine brain.

The content of gangliosides and sialosylglycoproteins was investigated in a coated-vesicle-enriched fraction prepared from bovine brain by the method of Pearse [(1975) J. Mol. Biol. 97, 93-98] and further purified by g.p.c. (glass-permeation chromatography) [Pfeffer & Kelly (1981) J. Cell Biol. 91, 385-391]. From morphological criteria and from the analysis of the polypeptide pattern on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis the coated-vesicle fraction (CV-fraction) appeared more than 95% pure. The ganglioside-NeuAc (N-acetylneuraminate), glycoprotein-NeuAc, phospholipid and cholesterol contents of CV-fraction were compared with those of bovine brain synaptic plasma membranes (SPM). The cholesterol to phospholipid molar ratio was 0.47 +/- 0.07 in CV-fraction and 1.06 +/- 0.08 in SPM. The ganglioside-NeuAc and glycoprotein-NeuAc to phospholipid molar ratios were 0.047 and 0.020 respectively in CV-fraction and 0.039 and 0.016 respectively in SPM. The (Na+ + K+)-dependent ATPase activity sensitive to ouabain (in mumol of Pi/h per nmol of phospholipid) was 1.04 in CV-fraction and 0.63 in SPM; the ratio between this activity and the activity resistant to ouabain was 2 in CV-fraction and 1.4 in SPM. A t.l.c. analysis of the ganglioside fractions showed that most of the ganglioside species present in SPM were present in CV-fraction. In a rat brain coated-vesicle preparation not subjected to g.p.c., the activities [as sugar-radioactivity (c.p.m.) transferred/h per mumol of phospholipid] of the enzymes CMP-NeuAc:sialosyl-lactosylceramide (GM3) sialosyl-, UDP-Gal:N-acetylgalactosaminyl(sialosyl)lactosylceramide (GM2) galactosyl- and UDP-GalNAc:sialosyl-lactosylceramide (GM3) N-acetylgalactosaminyl-transferases, which were considered Golgi-apparatus markers, were about 19, 16 and 10% respectively of those determined in rat brain neuronal perikaryon-enriched fractions. Taken together, the results indicate that most of the major gangliosides are constituents of coated vesicles.

Adenosine Triphosphatases↗
PubMed1986

Determination of gangliosides as 2,4-dinitrophenylhydrazides by high-performance liquid chromatography.

A specific, sensitive and easily performed method for the determination of gangliosides in tissue was developed. After removal of water-soluble compounds, total lipids were extracted from tissue and then treated with 2,4-dinitrophenylhydrazine hydrochloride and dicyclohexylcarbodi-imide in dimethylformamide at 0 degrees C to form ganglioside hydrazides. After removal of excess reagents by column chromatography on silicic acid, the ganglioside 2,4-dinitrophenylhydrazides were eluted from the column and analysed by h.p.l.c. with the use of a silica-gel normal-phase column eluted with an isocratic chloroform/methanol/water/acetic acid system. The addition of CaCl2 improved the separation of GM3 ganglioside containing N-acetylneuraminic acid from that containing N-glycollylneuraminic acid. 2,4-Dinitrophenylhydrazide peaks were measured by the absorbance at 342 nm. Quantification of GM3, GM2, GM1, GD1a, GD1b, GT1b and LM1 gangliosides was linear in a range 0.02-1.6 nmol. GM4, GD3, GT1a and GQ1b gangliosides also yielded distinct peaks, although the range of linearity was not examined. This method was applied to the analysis of the total lipids of rat brain and hepatocytes.

Animals↗
PubMed1987

The sialic acid residue of exogenous GM1 ganglioside is recycled for biosynthesis of sialoglycoconjugates in rat liver.

In order to assess metabolic recycling of sialic acid, GM1 ganglioside [nomenclature of Svennerholm (1964) J. Lipid. Res. 5, 145-155; IUPAC-IUB Recommendations (1977) Lipids 12, 455-468], 14C-radiolabelled at the acetyl group of sialic acid, was intravenously injected into Wistar rats, and the presence of radioactive sialic acid in liver sialoglycolipids (gangliosides) and sialoglycoproteins was ascertained. A time-course study (20 min-72 h) showed that the radioactivity present in the liver distributed in the following fractions, with reciprocal proportion varying with time: the protein (glycoprotein) fraction, the ganglioside fraction and the diffusible fraction, which contained low-Mr compounds, including sialic acid. Ganglioside-linked radioactivity gradually decreased with time; protein-linked radioactivity appeared soon after injection (20 min), reached a maximum around 20 h, then slowly diminished; diffusible radioactivity provided a sharp peak at 4 h, then rapidly decreased till disappearing after 40 h. The behaviour of bound radioactivity in the individual liver gangliosides was as follows: (a) rapid diminution with time in GM1, although with a lower rate at the longer times after injection; (b) early appearance (20 min) with a peak at 1 h, followed by continuous diminution, in GM2; (c) early appearance (20 min), peak at 1 h, diminution till 4 h, followed by a plateau, in GM3; (d) appearance at 60 min, maximum around 40 h and slow diminution thereafter, in GD1a, GD1b and GT1b. A detailed study, accomplished at 40 h after injection, demonstrated that almost all radioactivity present in the protein fraction was released by mild acid treatment and recovered in purified sialic acid; most of radioactive glycoprotein-bound sialic acid was releasable by sialidase action. In addition, the radioactivity present in the different gangliosides was exclusively carried by sialic acid and present in both sialidase-resistant and sialidase-labile residues. Only in the case of GD1a was the specific radioactivity of sialidase-resistant sialic acid superior to that of sialidase-releasable sialic acid. The results obtained lead to the following conclusions: (a) radioactive GM3 and GM2 were produced by degradation of GM1 taken up; GM3 originated partly by a process of neosynthesis; (b) radioactive GM1 consisted in part of residual exogenous GM1 and in part of a neosynthetized product; (c) radioactive GD1a originated in part by direct sialylation of GM1 taken up and in part by a neosynthetic process; (d) radioactive GD1b and GT1b resulted only from neosynthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Ganglioside incorporation and release by the isolated perfused rat liver.

The fate of exogenous ganglioside GM1 labelled in the sphingosine moiety, [Sph-3H]GM1, administered as a pulse, in the isolated perfused rat liver was investigated. When a non-recirculating protocol was employed, the amount of radioactivity in the liver and perfusates was found to be dependent on the presence of BSA in the perfusion liquid and on the time elapsed after the administration of the ganglioside. When BSA was added to the perfusion liquid, less radioactivity was found in the liver and more in the perfusate at each time tested, for up to 1 h. The recovery of radioactivity in the perfusates followed a complex course which can be described by three pseudo-first-order kinetic constants. The constants, in order of decreasing velocity, are interpreted as: (a) the dilution of the labelled GM1 by the constant influx of perfusion liquid; (b) the washing off of GM1 loosely bound to the surface of liver cells; (c) the release of gangliosides from the liver. Process (b) was found to be faster in the presence of BSA, probably owing to the ability of BSA to bind gangliosides. The [Sph-3H]GM1 in the liver underwent metabolism, leading to the appearance of products of anabolic (GD1a, GD1b) and catabolic (GM2, GM3) origin; GD1a appeared before GM2 and GM3 but, at times longer than 10 min, GM2 and GM3 showed more radioactivity than GD1a. At a given time the distribution of the radioactivity in the perfusates was quite different from that of the liver. In fact, after 60 min GD1a was the only metabolite present in any amount, the other being GM3, the quantity of which was small. This indicates that the liver is able to release newly synthesized gangliosides quite specifically. When a recirculating protocol was used, there were more catabolites and less GD1a than with the non-recirculating protocol. A possible regulatory role of ganglioside re-internalization on their own metabolism in the liver is postulated.

Animals↗
PubMed2004

The HCC-domain of botulinum neurotoxins A and B exhibits a singular ganglioside binding site displaying serotype specific carbohydrate interaction.

Tetanus and botulinum neurotoxins selectively invade neurons following binding to complex gangliosides. Recent biochemical experiments demonstrate that two ganglioside binding sites within the tetanus neurotoxin HC-fragment, originally identified in crystallographic studies to bind lactose or sialic acid, are required for productive binding to target cells. Here, we determine by mass spectroscopy studies that the HC-fragment of botulinum neurotoxins A and B bind only one molecule of ganglioside GT1b. Mutations made in the presumed ganglioside binding site of botulinum neurotoxin A and B abolished the formation of these HC-fragment/ganglioside complexes, and drastically diminished binding to neuronal membranes and isolated GT1b. Furthermore, correspondingly mutated full-length neurotoxins exhibit significantly reduced neurotoxicity, thus identifying a single ganglioside binding site within the carboxyl-terminal half of the HC-fragment of botulinum neurotoxins A and B. These binding cavities are defined by the conserved peptide motif H...SXWY...G. The roles of tyrosine and histidine in botulinum neurotoxins A and B in ganglioside binding differ from those in the analogous tetanus neurotoxin lactose site. Hence, these findings provide valuable information for the rational design of potent botulinum neurotoxin binding inhibitors.

Amino Acid Sequence↗
PubMed2000

Evidence that ganglioside enriched domains are distinct from caveolae in MDCK II and human fibroblast cells in culture.

Cultures of MDCK II and human fibroblast cells were fed radioactive sphingosine and a radioactive GM3 ganglioside derivative containing a photoactivable group. The derived cell homogenates were treated with Triton X-100 and fractionated by sucrose-gradient centrifugation to prepare a detergent-insoluble membrane fraction known to be enriched in sphingolipid and caveolin-1, i.e. of caveolae. The detergent-insoluble membrane fraction prepared after feeding [1-3H]sphingosine to cells, was found to be highly enriched, with respect to protein content, in metabolically radiolabeled sphingomyelin and glycosphingolipids (about 18-fold). By feeding cells photoactivable radioactive GM3, after 2 h-chase, caveolin-1, CAV1, and proteins of high molecular mass became cross-linked to GM3, the cross-linking complexes being highly concentrated in the detergent-insoluble membrane fraction. The interaction between the ganglioside derivative and CAV1 was a time-dependent, transient process so that CAV1 cross-linking to GM3 was hardly detectable after a 24-h chase followed the pulse time. After a 24-h chase, only the high molecular mass proteins cross-linked to GM3 could be clearly observed. These results suggest that a portion of the GM3 administered to cells enters caveolae and moves to the glycosphingolipid domains, or enters caveolae that are then rapidly catabolized. Electron microscopy of cells in a culture immunostained with a monoclonal antibody to GM3 and a secondary gold-conjugated antibody detected several clusters of gangliosides on the plasma membranes separate from caveolae; gangliosides located inside the caveolae could not be detected. Scanning confocal microscopy of cells immunostained with anti-GM3 and anti-CAV1 Ig showed only a very small overlap with the CAV1 and GM3 signals. Thus, the biochemical and microscopic studies suggest that caveolae contain at most a low level of gangliosides and are separate from the GM3 ganglioside enriched domains.

Animals↗
PubMed1999

Relationship of glycosyltransferases and mRNA levels to ganglioside expression in neuroblastoma and melanoma cells.

Most human neuroblastoma tumors are characterized by the high expression of GD2 (or GD2 and/or GM2) gangliosides, whereas melanomas characteristically express GD3 ganglioside. The molecular basis for these patterns was investigated by examining the relationship between ganglioside levels, glycosyltransferase (GM2/GD2 synthase and GD3 synthase) activity, and corresponding mRNA levels in a panel of human neuroblastoma and melanoma cell lines. In general, the ganglioside patterns could be explained by the levels of the transferases and their mRNA, indicating control at the level of transcription. A key role was noted for GD3 synthase. Notably, it was found that neuroblastoma cell lines with high GD2 ganglioside levels had low levels of GD3, its synthase, and mRNA for the enzyme even though this step provides the substrate for GD2 synthesis. The key role for GD3 synthase was also examined by stably transfecting GD3 synthase cDNA into a neuroblastoma cell line (SH-SY5Y) not expressing GD3 and GD2. The resulting cell line had high levels of GD2 ganglioside and altered morphology and growth characteristics.

Blotting, Northern↗
PubMed2001

Ganglioside modulates ligand binding to the epidermal growth factor receptor.

Whereas previous investigations have shown that pharmacologic addition of gangliosides inhibits keratinocyte proliferation by downregulating epidermal growth factor receptor phosphorylation, the underlying biochemical basis and physiologic relevance are unknown. Using Scatchard and displacement plots, we have shown that supplemental purified gangliosides decrease the binding of (125)I-labeled epidermal growth factor to keratinocyte-derived SCC12 cells. Conversely, SCC12 cells transfected with sialidase and thus depleted of gangliosides show increased ligand binding to the epidermal growth factor receptor, which is consistent with their increased proliferation in response to epidermal growth factor and transforming growth factor-alpha, and increased phosphorylation of the epidermal growth factor receptor, and downstream signal transduction pathway components. The mechanism of the altered binding appears to involve primarily decreased numbers of available receptors within the intact membrane, but not altered receptor protein expression. These studies provide evidence that the effect of gangliosides on keratinocyte proliferation results, at least in part, from the direct binding of ganglioside to the receptor and disruption of the receptor-ligand interaction. Manipulation of membrane ganglioside content may be a powerful new means to alter epidermal growth factor receptor-dependent cell proliferation.

DNA, Complementary↗
PubMed2001

Detection of sialic acids and gangliosides with special reference to 9-O-acetylated species in basaliomas and normal human skin.

Basal cell carcinomas and normal skin were examined in relation to the abnormal expression of gangliosides. The content of gangliosides with 9-O-acetylated sialic acids of 26 sample pairs was analyzed by a microtiter assay using influenza C virus as well as by fluorimetric high-performance liquid chromatography of the sialic acids released. The 9-O-acetylation levels were significantly (up to 56-fold) higher in basal cell carcinoma tissues than in the skin surrounding basal cell carcinomas. Slightly elevated amounts of O-acetylated gangliosides were also seen in the skin marginal to the basaliomas. The ganglioside composition of four sets of pooled samples of basal cell carcinoma and one pool of normal skin were studied by high-performance thin-layer chromatography and immune high-performance thin-layer chromatography using monoclonal antibodies against 9-O-acetyl GD3. The lipid-bound sialic acid content of normal skin was 0.029 microg dry weight, whereas in nodular basal cell carcinomas it was approximately twice as much. Several O-acetylated sialic acids were seen by high-performance liquid chromatography analysis, but N-acetyl-9-O-acetylneuraminic acid prevailed. Only in the tumor ganglioside fraction, a small amount of N-glycolylneuraminic acid was found. The 9-O-acetylated gangliosides with mainly 9-O-acetyl-GD3 can be considered as tumor-associated antigens or markers for basal cell carcinomas. This finding about tumor-associated carbohydrates may contribute to new strategies in current tumor diagnosis and therapy.

Acetylation↗
PubMed2005

Interruption of ganglioside synthesis produces central nervous system degeneration and altered axon-glial interactions.

Gangliosides, which are sialylated glycosphingolipids, are the major class of glycoconjugates on neurons and carry the majority of the sialic acid within the central nervous system (CNS). To determine the role of ganglioside synthesis within the CNS, mice carrying null mutations in two critical ganglioside-specific glycosyltransferase genes, Siat9 (encoding GM3 synthase) and Galgt1 (encoding GM2 synthase), were generated. These double-null mice were unable to synthesize gangliosides of the ganglio-series of glycosphingolipids, which are the major ganglioside class in the CNS. Soon after weaning, viable mice developed a severe neurodegenerative disease that resulted in death. Histopathological examination revealed striking vacuolar pathology in the white matter regions of the CNS with axonal degeneration and perturbed axon-glia interactions. These results indicate that ganglioside synthesis is essential for the development of a stable CNS, possibly by means of the promotion of interactions between axon and glia.

Animals↗
PubMed2002

Cell membrane GM1 ganglioside is a functional coreceptor for fibroblast growth factor 2.

Free gangliosides bind fibroblast growth factor 2 (FGF2), thus preventing cell interaction and biological activity of the growth factor in endothelial cells. Here we investigated the role of cell-associated gangliosides in mediating the biological activity of FGF2. Treatment of endothelial cells of different origin with the ganglioside biosynthesis inhibitors fumonisin B1, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol or D-1-threo-1-phenyl-2-hexa-decanoylamino-3-pyrrolidino-1-propanol-HCl, impairs their capacity to proliferate when exposed to FGF2. Also, the mitogenic activity of FGF2 is inhibited by the GM1-binding cholera toxin B subunit (CTB). Conversely, overloading of endothelial GM 7373 cell membranes with exogenous GM1 causes a 10-fold increase of the mitogenic potency of FGF2. 125I-FGF2 binds to cell membrane GM1 (K(d) = 3 nM) in complex ganglioside/heparan sulfate-deficient Chinese hamster ovary (CHO)-K1-pgsA745 cell mutants that were overloaded with exogenous GM1. Moreover, FGF2 competes with FITC-CTB for the binding to cell membrane GM1 in different CHO cell lines independently of their capacity to express heparan sulfate proteoglycans. Conversely, CTB inhibits cell proliferation triggered by FGF2 in CHO cells overexpressing the tyrosine kinase FGF receptor 1. Finally, GM1-overloading confers to FGF receptor 1-transfected, complex ganglioside-deficient CHO-K1 cell mutants the capacity to proliferate when stimulated by FGF2. This proliferation is inhibited by CTB. Cell proliferation triggered by serum or by phorbol 12-myristate 13-acetate is instead independent of the cell membrane ganglioside milieu. In conclusion, cell membrane GM1 binds FGF2 and is required for the mitogenic activity of the growth factor. Our data indicate that cell-associated gangliosides may act as functional FGF2 co-receptors in different cell types.

Animals↗
PubMed1980

Sendai virus receptor: proposed recognition structure based on binding to plastic-adsorbed gangliosides.

The binding of Sendai virus to polystyrene petri dishes to which various gangliosides of defined structures had been adsorbed was determined. The ganglioside-bound virus was visualized either by a water vapor condensation method or by a hemadsorption method. By either assay, specific virus binding of high affinity was demonstrated to the gangliosides GT1a, GQ1b, and GPlc which have a common end sequence in the oligosaccharide moiety: NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc leads to. Binding also occurred to the GD1a and GT1b gangliosides, which have the same end carbohydrate sequence except for the terminal N-acetylneuraminic acid, but the affinity was only 1-9% of that of the gangliosides with a terminal disialosyl linkage. It is proposed that the structure NeuAc alpha 2 leads to 8NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc is the recognition-specific structure of the receptor for Sendai virus that is present on cell membrane gangliosides and possibly also glycoproteins. Binding tests to plastic-adsorbed glycolipids are suggested to be a useful tool for identification of the receptor recognition structure.

Adsorption↗
PubMed1983

Tunicamycin inhibits ganglioside biosynthesis in neuronal cells.

The antibiotic tunicamycin blocks the transfer of GlcNAc-1-P from UDP-GlcNAc to dolichol phosphate, thereby blocking the synthesis of N-linked oligosaccharide chains on glycoproteins. Its effect on the biosynthesis of gangliosides has not been reported. We report that tunicamycin caused a 70-80% reduction in incorporation of [(3)H]GlcN into gangliosides and neutral glycosphingolipids of the neuroblastoma-glioma hybrid cell line NG 108-15 at antibiotic concentrations that caused a 90% reduction of the radiolabel incorporation into glycoproteins. The effect of tunicamycin on ganglioside biosynthesis was apparent after only 4 hr of incubation, and maximum inhibition was seen within 6 hr. When control or tunicamycin-treated (5 mug/ml) cells were collected and fractionated to separate glycoproteins, neutral glycosphingolipids, gangliosides, and nucleotide sugar-precursor pools, the following results were obtained: (i) UDP-GlcNAc and UDP-GalNAc pool sizes increased >3-fold, and specific activities decreased 50% upon treatment with tunicamycin; (ii) when corrected for this value, the percentage inhibition of GlcN incorporation into various glycoconjugates by tunicamycin in these cells was 82% for glycoproteins, 54% for neutral glycosphingolipids, and 50% for gangliosides; and (iii) the different gangliosides were affected differentially, with the most striking inhibition apparent in GM(3) biosynthesis, which was decreased 78% in the presence of tunicamycin. These data suggest that the effects of tunicamycin on glycosphingolipids as well as on glycoproteins must be considered when interpreting its effects on intact cells and organisms.

Acetylglucosamine↗
PubMed1991

Ectopic dendrites occur only on cortical pyramidal cells containing elevated GM2 ganglioside in alpha-mannosidosis.

In a variety of neuronal storage diseases, cortical pyramidal cells elaborate ectopic dendrites at the axon hillock. A feature common to all the diseases characterized by ectopic dendrites is an elevated level of GM2 ganglioside in cerebral cortex. In cats with one such disease, alpha-mannosidosis, the number of pyramidal cells bearing ectopic dendrites is small; the present study shows that GM2 ganglioside is stored only in those pyramidal neurons exhibiting ectopic dendrites. Using a Golgi-electron microscopy method with periodic acid-Schiff (PAS) staining, we first established that pyramidal cells bearing ectopic dendrites contained PAS+ membranous inclusions, consistent with storage of glycolipids. In contrast, those with smooth axon hillocks accumulated PAS- floccular inclusions, consistent with storage of oligosaccharides. Next, application of a monoclonal antibody against GM2 ganglioside revealed that subsets of both pyramidal and intrinsic neurons contained GM2-like immunoreactivity. Every GM2+ cell contained PAS+ membranous inclusions, indicating that pyramidal cells bearing ectopic dendrites stored GM2 ganglioside. In cats with alpha-mannosidosis induced by swainsonine, some pyramidal neurons showed GM2-like immunoreactivity after 4 weeks of treatment, whereas ectopic dendrites only became evident after 7 weeks of treatment. Thus, GM2 ganglioside accumulated in pyramidal neurons before ectopic dendrites emerged from the axon hillock. We propose that the reinitiation of dendrite growth on mature pyramidal cells is brought about by accumulated GM2 ganglioside.

Animals↗
PubMed1994

Modulation by gangliosides of the lamellar-inverted micelle (hexagonal II) phase transition in mixtures containing phosphatidylethanolamine and dioleoylglycerol.

We studied the effect of gangliosides GD1a and GM1 on the lamellar-to-hexagonal II phase transition of mixtures of dioleoylphosphatidylethanolamine/dioleoylphosphatidyl choline, 3:1, and of transphosphatidylated phosphatidylethanolamine with dioleoylglycerol by high-sensitivity differential scanning calorimetry, 31P-NMR, and pyrene fluorescence of a phosphatidylcholine probe. Gangliosides had a dual effect. Below 1 mol % ganglioside the hexagonal II phase transition was affected but still occurred at lower temperature than in the absence of gangliosides. The presence of between 1 and 2 mol % gangliosides increased the temperature for formation of the hexagonal II phase and progressively decreased its cooperativity. Above 3 mol % gangliosides totally inhibited the formation of both the temperature-induced and composition-induced hexagonal phase, probably by opposing the geometric distortions necessary for the inverted micellar structures.

Diglycerides↗