Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Globosides”

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 163 records · Page 9Linked to original sources
PubMed1979

Isolation and partial characterization of the neutral glycosphingolipids and gangliosides of the human heart.

The glycosphingolipids (GSL) of the human heart muscle have been isolated from total lipids by column and thin layer chromatography and their sugars and fatty acids analyzed by gas liquid chromatography. Hearts from traffic victims were obtained at autopsy between 12 and 16 hr after death and dissected into parts (left and right ventricular walls, intraventricular septum and papillary muscle). The neutral GSL content for those parts of the hearts of two males aged 22 and one female aged 14 ranged from about 90 to 160 nmoles/g wet weight. Trihexosyl ceramide and globoside were the most abundant neutral GSL. Total ganglioside content was about 50 nmoles/g wet weight, and the most abundant gangliosides were partially characterized as GM3 and GM1; other mono-, di- and trisialogangliosides were also present. Differences in the content and composition of neutral GSL and gangliosides between the heart and other human tissues are discussed. It is concluded that the patterns of these two GSL fractions of the heart are more complex than those of the extraneural human tissues.

Adult↗
PubMed1992

Neutral glycolipids of human and bovine milk.

The neutral glycolipids of milk, a small fraction of the total lipids, are of potential biological importance. The simultaneous quantitation of the simple (less than five sugars) glycosphingolipids of human milk samples was achieved by high-pressure liquid chromatography. The samples, representing various stages of lactation, parity of the nursing child, and age of the mother, contained similar glycolipid patterns, but with varying individual glycolipid concentrations. The cerebrosides are major glycosphingolipids of human milk: the non-hydroxylated fatty acid (NFA)-containing species are present at 1.8 microM, and the hydroxylated and/or short-chain fatty acid-containing species (HFA) are present at 1.7 microM; NFA lactosylceramide is present at 931 nM. The cerebrosides appear to be primarily galactosylceramides (galactocerebrosides); glucosylceramides (glucocerebrosides) are a minor component. Globotriaosylceramide (Gb3) is found at 50 nM and 73 nM for the NFA and HFA species, respectively, while globoside (Gb4) is found at 45 nM and 46 nM for the NFA and HFA species. Bovine milk glycosphingolipids differ from those of human milk, with bovine milk containing mainly NFA glucosylceramide (8 microM) and NFA lactosylceramide (17 microM); bovine milk contains little Gb3 or Gb4.

Animals↗
PubMed2006

Presence of natural anti-Galalpha1-4GalNAcbeta1-3Gal (anti-NOR) antibodies in animal sera.

Rare polyagglutinable NOR erythrocytes contain unusual globoside extention products terminating with a Galalpha1-4GalNAcbeta1-3Gal- unit. This trisaccharide epitope is recognized by recently characterized antibodies naturally occurring in most human sera (Duk et al., Glycobiology, 15, 109, 2005). These antibodies represent two major types of fine specificity. All these antibodies are most strongly inhibited by Galalpha1-4GalNAcbeta1-3Gal (NOR-tri), and weakly by Galalpha1-4Gal. However, the type 1 antibodies are strongly inhibited by Galalpha1-4Galbeta1-3Gal-R and weakly by Galalpha1-4GalNAc, while the type 2 antibodies show the opposite reactivities with these two oligosaccharides. Similar antibodies have now been found in horse, rabbit and pig sera. The antibodies were purified from animal sera by affinity chromatography on Galalpha1-4GalNAcbeta1-3Gal-human serum albumin(HSA)-Sepharose 4B conjugate. The specificity of the antibodies was determined by binding to ELISA plates coated with several alpha-galactosylated oligosaccharide-polyacrylamide (PAA) or -HSA conjugates and by inhibition with synthetic oligosaccharides. The purified antibodies bound specifically to conjugates containing NOR-tri. The inhibition of binding showed that the animal sera also contain two types of anti-NOR antibodies: type 2 was found in the horse serum, and a mixture of both types was present in rabbit and pig serum. These results indicate that anti-NOR, a new and distinct kind of anti-alphaGal antibody, are present in animal sera and show similar specificties and diversity as their counterparts found in human sera.

ABO Blood-Group System↗
PubMed1987

Analysis of NMR spectra of sugar chains of glycolipids by multiple relayed COSY and 2D homonuclear Hartman-Hahn spectroscopy.

We applied multiple relayed COSY and 2D homonuclear Hartman-Hahn spectroscopy to globoside, a glycolipid purified from human red blood cells. The subspectra corresponding to individual sugar components were extracted even from overlapping proton resonances by taking the cross sections of 2D spectra parallel to the F2 axis at anomeric proton resonances, so that unambiguous assignments of sugar proton resonances were accomplished.

Galactosamine↗
PubMed1991

Decreased biosynthesis of Forssman glycolipid after retinoic acid-induced differentiation of mouse F9 teratocarcinoma cells. Lectin-affinity chromatography of the glycolipid-derived oligosaccharide.

Glycolipids synthesized by the mouse teratocarcinoma F9 cells and F9 cells (RA/F9 cells) induced to differentiate by a 3-day treatment with 0.1 microM all-trans-retinoic acid were analyzed. Both F9 cells and RA/F9 cells were incubated in media containing either D-[6-3H]galactose or D-[6-3H]glucosamine; the metabolically-radiolabeled glycolipids were isolated and the oligosaccharides were released from the glycolipids by ozonolysis and alkali fragmentation. From both cells, a single major pentasaccharide was isolated from the mixture of neutral [3H]oligosaccharides by affinity chromatography on a column of immobilized Helix pomatia agglutinin. The structure of this oligosaccharide was analyzed by methylation analysis and specific exoglycosidase treatments and identified as the Forssman pentasaccharide alpha-D-GalpNAc-(1----3)-beta-D-GalpNAc-(1----4)-alpha-D-Galp-(1----4)-b eta-D- Galp-(1----4)-D-Glc. There was a 3-4-fold decreased amount of the Forssman pentasaccharide from RA/F9 cells relative to F9 cells. In contrast, there were no major differences between these cells in the levels of globoside, the precursor to Forssman glycolipid. To investigate the basis for the decline in Forssman glycolipid synthesis upon differentiation, the activity of UDP-D-Gal-NAc:GbOse4Cer alpha-(1----3)-N-acetyl-D-galactosaminyltransferase (Forssman synthase) was determined in extracts of both the F9 and RA/F9 cells. The specific activity of Forssman synthase was approximately 70% lower in differentiated relative to the nondifferentiated cells. These data demonstrated that F9 cells synthesize authentic Forssman glycolipid, and that its expression and the activity of Forssman synthase were decreased following induced cellular differentiation.

Animals↗
PubMed2001

Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor.

PapG is the adhesin at the tip of the P pilus that mediates attachment of uropathogenic Escherichia coli to the uroepithelium of the human kidney. The human specific allele of PapG binds to globoside (GbO4), which consists of the tetrasaccharide GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc linked to ceramide. Here, we present the crystal structures of a binary complex of the PapG receptor binding domain bound to GbO4 as well as the unbound form of the adhesin. The biological importance of each of the residues involved in binding was investigated by site-directed mutagenesis. These studies provide a molecular snapshot of a host-pathogen interaction that determines the tropism of uropathogenic E. coli for the human kidney and is critical to the pathogenesis of pyelonephritis.

Adhesins, Escherichia coli↗
PubMed1997

Report on a patient with paroxysmal cold hemoglobinuria.

Antibodies against the human blood group P antigen (anti-P alloantibodies) agglutinate phenotype P1 and P2 erythrocytes treated with papain at 4 degrees C but not phenotype PK and p erythrocytes. This condition is referred to as an autoimmune disease of paroxysmal cold hemoglobinuria (PCH), and the anti-P specificity is found in the cold hemagglutinins. Serum from a patient suspected to be suffering from PCH by the cold auto-agglutination properties was tested for anti-P specificity, using papain-treated O blood group erythrocytes. The serum-mediated hemagglutination and the serum and complement-mediated immunohemolysis were inhibited by globoside (P antigen GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-ceramide) and Forssman glycosphingolipid (GalNAc alpha 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-ceramide). Therefore, we concluded that she had PCH. She was completely cured 6 months later.

Female↗
PubMed2004

Expression of neutral glycosphingolipids in cytokine-stimulated human endothelial cells.

We compared immunohistochemical distribution of glycosphingolipids globotriosylceramide (GbOse(3)Cer) and globotetraosylceramide (GbOse(4)Cer) with that of E-selectin on human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor (TNF)-alpha. HUVECs activated by TNF-alpha were characterized by the highest expression of E-selectin and greatest adhesion of HL-60 cells as well compared to stimulation with interleukin-1beta or lipopolysaccharide. HUVECs activated by TNF-alpha also stained intensely with globoside antibodies, especially with the GbOse(3)Cer-directed one, staining being redistributed in a concentration-dependent manner. These results indicate the possible role of GbOse(3)Cer and GbOse(4)Cer in immune effector mechanisms of endothelium such as adhesion.

Cell Adhesion↗
PubMed2000

Glycosphingolipid composition of a new immortalized human cerebromicrovascular endothelial cell line.

Previous studies have demonstrated the involvement of glycosphingolipid (GSL) antigens in the pathogenesis of immune-mediated neurological disorders such as peripheral neuropathies and multiple sclerosis. To study the role of the blood-brain barrier (BBB) in these disorders, we used a new human cerebromicrovascular endothelial cell (HCEC) line that has been immortalized through transfection with the plasmid pSV3-neo encoding for the SV40 large T-antigen and the neomycin gene. The immortalized HCEC (SV-HCEC) exhibited accelerated proliferation rates but maintained phenotypic properties of early-passage control cells. Therefore, this human cell line may serve as a useful in vitro model for studying the properties of the human BBB. We first investigated the GSL composition of cultured SV-HCECs. The major gangliosides were GM3 (62% of total gangliosides), GM2 (18%), GM1 (3%), and GD1a (15%). The major neutral GSLs were glucosylceramide (15% of the total neutral glycolipids), lactosylceramide (36%), globotriaosylceramide (3%), and globoside (43%). Trace amounts of paragloboside, lactosaminyl paragloboside, and sulfoglucuronyl paragloboside could also be detected by TLC-immunostaining. These results provide the basis for further investigations of the expression of these cell surface antigens in cultured SV-HCECs on activation with inflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma, which have been implicated as playing an important role in the pathogenesis of many nervous system disorders.

Blood-Brain Barrier↗
PubMedDate not supplied

Autoagglutinins with apparent anti-P specificity reactive only by low-ionic-strength salt techniques.

Two blood samples containing autoagglutinins reactive in room temperature tests using low-ionic strength salt (LISS) reagents, but not by conventional saline-albumin or enzyme tests, are reported. The anti-P specificity of both sera, when tested near or diluted in group AB serum, was evident by their failure to agglutinate LISS-suspended Tj(a-),(p), and P1 red blood cells. However, one of the two samples displayed no anti-P specificity when diluted in LISS solution as opposed to group AB serum. Some urine samples inhibited this latter serum. Inhibition did not correlate with urinary Sda antigen content, nor with pH, Na+, K+, C1-, or osmolality levels. However, there was some correlation between inhibition and urinary conductivity levels. Moreover, partial inhibition was observed in tests with globoside. While there are no data to indicate that these LISS-dependent autoagglutinins are of clinical consequence in vivo, it is likely that they represent low-affinity autoantibodies reacting only in a low-ionic environment. They establish a further cause of anomalous serologic reactions associated with LISS techniques.

Adolescent↗
PubMed2000

Cloning of Gb3 synthase, the key enzyme in globo-series glycosphingolipid synthesis, predicts a family of alpha 1, 4-glycosyltransferases conserved in plants, insects, and mammals.

We have cloned Gb(3) synthase, the key alpha1, 4-galactosyltransferase in globo-series glycosphingolipid (GSL) synthesis, via a phenotypic screen, which previously yielded iGb(3) synthase, the alpha1,3-galactosyltransferase required in isoglobo-series GSL (Keusch, J. J., Manzella, S. M., Nyame, K. A., Cummings, R. D., and Baenziger, J. U. (2000) J. Biol. Chem. 33). Both transferases act on lactosylceramide, Galbeta1,4Glcbeta1Cer (LacCer), to produce Gb(3) (Galalpha1,4LacCer) or iGb(3) (Galalpha1, 3LacCer), respectively. GalNAc can be added sequentially to either Gb(3) or iGb(3) yielding globoside and Forssman from Gb(3), and isogloboside and isoForssman from iGb(3). Gb(3) synthase is not homologous to iGb(3) synthase but shows 43% identity to a human alpha1,4GlcNAc transferase that transfers a UDP-sugar in an alpha1, 4-linkage to a beta-linked Gal found in mucin. Extensive homology (35% identity) is also present between Gb(3) synthase and genes in Drosophila melanogaster and Arabidopsis thaliana, supporting conserved expression of an alpha1,4-glycosyltransferase, possibly Gb(3) synthase, throughout evolution. The isolated Gb(3) synthase cDNA encodes a type II transmembrane glycosyltransferase of 360 amino acids. The highest tissue expression of Gb(3) synthase RNA is found in the kidney, mesenteric lymph node, spleen, and brain. Gb(3) glycolipid, also called P(k) antigen or CD77, is a known receptor for verotoxins. CHO cells that do not express Gb(3) and are resistant to verotoxin become susceptible to the toxin following transfection with Gb(3) synthase cDNA.

Amino Acid Sequence↗
PubMed2001

Clathrin-dependent and -independent internalization of plasma membrane sphingolipids initiates two Golgi targeting pathways.

Sphingolipids (SLs) are plasma membrane constituents in eukaryotic cells which play important roles in a wide variety of cellular functions. However, little is known about the mechanisms of their internalization from the plasma membrane or subsequent intracellular targeting. We have begun to study these issues in human skin fibroblasts using fluorescent SL analogues. Using selective endocytic inhibitors and dominant negative constructs of dynamin and epidermal growth factor receptor pathway substrate clone 15, we found that analogues of lactosylceramide and globoside were internalized almost exclusively by a clathrin-independent ("caveolar-like") mechanism, whereas an analogue of sphingomyelin was taken up approximately equally by clathrin-dependent and -independent pathways. We also showed that the Golgi targeting of SL analogues internalized via the caveolar-like pathway was selectively perturbed by elevated intracellular cholesterol, demonstrating the existence of two discrete Golgi targeting pathways. Studies using SL-binding toxins internalized via clathrin-dependent or -independent mechanisms confirmed that endogenous SLs follow the same two pathways. These findings (a) provide a direct demonstration of differential SLs sorting into early endosomes in living cells, (b) provide a "vital marker" for endosomes derived from caveolar-like endocytosis, and (c) identify two independent pathways for lipid transport from the plasma membrane to the Golgi apparatus in human skin fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Enzymatic transfer of a beta1,6-linked N-acetylglucosamine to the alpha-galactose of globo-N-tetraose: in vitro synthesis of a novel hybrid pentasaccharide of lacto-globo type.

A novel saccharide was synthesized by incubating globo-N-tetraose, GalNAc beta1-3Gal alpha1-4Gal beta1-4Glc, and UDP[3H]GlcNAc with hog gastric mucosal microsomes, known to contain beta1,6-N-acetylglucosaminyltransferase activity of a broad acceptor specificity. Chromatography and MALDI-TOF mass spectrometry of the product, as well as the amount of incorporated radioactivity indicated that one [3H]GlcNAc residue was transferred to the acceptor saccharide. One- and two-dimensional 1H NMR-spectroscopic analysis of the product and ESI-CID mass spectrometry of the pentasaccharide in permethylated form established its structure as GalNAc beta1-3([3H]GlcNAc beta1-6)Gal alpha1-4Gal beta1-4Glc. The new enzyme activity possesses substrate specificity features common to a purified beta1,6-GlcNAc-transferase from bovine tracheal epithelium, which forms branches at the subterminal beta1,3-substituted galactose and accepts both GlcNAc- and Gal-configuration at the terminal residue of the acceptor (Ropp et al. (1991) J. Biol. Chem., 266, 23863-23871). The new beta1,6-GlcNAc-branch was readily galactosylated by bovine milk beta1,4-galactosyltransferase, revealing a pathway to novel hybrid type glycans with N-acetyllactosamine chains on globotype saccharides. This pathway may lead to the rare IP blood-group antigen and to globoside-like molecules mediating cell adhesion.

Animals↗
PubMed1995

Multiple glycosphingolipids determine the tissue tropism of parvovirus B19.

Infection with human parvovirus B19, the etiologic agent of fifth disease, is associated with numerous hematologic and nonhematologic complications. Recently, the receptor for parvovirus B19 was reported to be globoside (Gb4), a neutral glycosphingolipid (GSL) of red cell membranes. To ascertain if tissue Gb4 expression correlates with B19-associated disease, neutral GSLs from 16 human tissues were isolated and analyzed using high-performance thin-layer chromatography and immunostaining with anti-Gb4 monoclonal antibodies or B19 empty capsids. Gb4 was identified as a major neutral GSL in 11 tissues, especially in those of mesodermal origin. In addition to recognizing Gb4, B19 capsid bound to several tissue-specific GSLs, including two complex globo series GSLs (SSEA-3, SSEA-4) and paragloboside (neolactotetraglycosylceramide), as was demonstrated in red cell, granulocyte, kidney, liver, and bowel tissue. There was good correlation between tissue-neutral GSL expression, B19 capsid binding, and the tissue tropism observed clinically in B19 parvovirus-associated disease.

Blood Cells↗
PubMed1980

Blood group type glycosphingolipids of human cord blood erythrocytes.

The non-acid glycosphingolipids of cord blood erythrocytes, pooled from blood groups O and A respectively, were characterized by mass spectrometry in combination with immunologic and thin-layer chromatographic analyses. The glycosphingolipid pattern was compared to that of adult erythrocytes. Just as for adult blood, the major glycosphingolipid species were lactosylceramide and globotetraosylceramide (globoside). The triglycosylceramide fraction was quantitatively smaller in cord red blood cells and was also enriched in a triglycosylceramide with a terminal hexosamine, as conclusively shown by mass spectrometry. The amount of blood group A and H active glycosphingolipids appeared to be less in cord blood cells compared to adult cells was glycolipids with longer, probably branched chain structures were not detected. In contrast, increased amounts of penta- and hexaglycosylceramides lacking fucose and possibly being biosynthetic precursor substances to the ordinary blood group A and H glycosphingolipids were found typical for cord blood cells.

ABO Blood-Group System↗
PubMed1979

Immunological identification of blood group Pk antigen on normal human erythrocytes and isolation of anti-Pk with different affinity.

The P1 and Pk blood group glycolipid antigens have the common terminal disaccharide, Gal(alpha, 1-4)Gal, but previous studies indicated that anti-P1 from P2 individuals does not cross-react with Pk antigen. In this paper, the specificities of anti-P1 and anti-Pk were analyzed carefully by complement fixation and hemagglutination techniques and the following results were obtained: (1) Anti-P1 from P2 serum was not absorbed with the Pk glycolipid (CTH), but this antigen absorbed all anti-P1 and anti-Pk (anti-P1Pk) antibodies from the sera of four p individuals. Most of the anti-P1Pk antibodies were IgG, but the anti-p1 from the P2 individual was IgM. (2) The Pk antigen on normal P2 erythrocytes was not 'cryptic'. It was reactive with p serum from which the anti-P antibodies were removed by absorption with the P glycolipid (globoside). This was not appreciated previously because, in order to make anti-Pk reagents, p sera (anti-P1PPk) were absorbed with P1 cells which contain CTH. (3) The anti-P1Pk antibodies in p sera were separated by partial absorption with P1 erythrocytes and elution from the absorbing cells, into two fractions that differ markedly in their affinity for alpha-methyl-D-galactoside and the oligosaccharides prepared from CTH.

Absorption↗
PubMed1989

Neutral glycolipids of atherosclerotic plaques and unaffected human aorta tissue.

The composition, structure and localization of neutral glycosphingolipids of human aorta taken from subjects who had died after myocardial infarction were studied. Individual glycosphingolipids were purified by high-performance liquid chromatography and were characterized on the basis of their chromatographic mobility, carbohydrate composition, methylation analysis and by 1H-NMR spectroscopy. The main aortic glycosphingolipids were identified as glucosylceramide, lactosylceramide, globotriaosylceramide and globotetraosylceramide. Significant differences in the neutral glycosphingolipid composition of intima and media were detected. The neutral glycosphingolipid profile of medial plaques resembled that of unaffected media; however, significant differences were detected between intimal plaques and unaffected intima. Whereas the latter contained trihexosylceramide and globoside as the only neutral glycolipids, the intimal plaque glycolipids consisted mainly of glucosylceramide and also contained appreciable amounts of lactosylceramide which were completely absent in the unaffected intima. In comparison to intimal plaques, unaffected intima is characterized by a much higher content of cerebrosides terminating by beta-galactosyl residues which are known to interact with growth factors and other external stimuli. It thus seems possible that the proliferative activity of smooth muscle cells in atherosclerotic diseases is to some extent associated with their neutral glycolipid profile.

Adult↗
PubMed1981

Sandhoff disease.

An autopsy case of Sandhoff disease in a 2-year-old boy is reported. Diagnosis was established by enzyme assay, which demonstrated total deficiency of hexosaminidase in the serum. Histochemical examination, using hematoxylin-eosin (H & E) and Luxol fast blue (LFB) stain, showed accumulation of LFB-positive material not only in cells of the cerebrum, cerebellum, spinal cord, and peripheral nervous system, but also in reticuloendothelial cells of the lymph nodes, spleen, thymus, and liver, in podocytes of renal glomeruli, in all types of renal tubular cells, in endothelial cells of small vessels, in fibroblasts, and in epithelial cells of the epididymis and ductus deferens. Electron microscopic examination showed that these deposits contained electrondense membranous bodies. Lipid analysis demonstrated a marked elevation of ganglioside GM2 and its asialo derivative in the brain and liver. Accumulation of globoside was found in the liver, kidney, and spleen. There was complete absence of hexosaminidase in the brain and liver.

Brain↗