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 145 records · Page 8Linked to original sources

Glycosphingolipid composition of MDA-MB-231 and MCF-7 human breast cancer cell lines.

Much evidence has shown that glycosphingolipids are involved in cellular recognition, regulation of cell growth, and metastasis. In the present study, the major glycosphingolipids of two widely studied human breast cancer cell lines were examined. The MCF-7 cell line has functional estrogen and EGF receptors, is dependent on estrogen and EGF for growth, and is uninvasive, while MDA-MB-231 cells are a model for more aggressive, hormone-independent breast cancer. There was twice as much neutral glycolipid in MCF-7 cells as in MDA-MB-231 cells. The major neutral glycolipids in MDA-MB-231 cells were identified as CTH and globoside. MCF-7 cells also contained as the major neutral glycolipids CTH as well as globoside and two other glycolipids which were tentatively identified as galactosylgloboside and fucosylgalactosylgloboside by exoglycosidase treatments. Conversely, the ganglioside content was four fold higher in MDA-MB-231 cells compared to MCF-7 cells. The abundant gangliosides in both cell lines were GM3, GM2, GM1, and GD1a. A minor monosialoganglioside was detected in MDA-MB-231 cells. The striking 18 fold greater amount of GM3 in MDA-MB-231 cells may have important implications because GM3 has been suggested to be involved in regulation of growth factor functions. In agreement, insertion of ganglioside GM3 into the plasma membrane of MCF-7 cells blocked the growth stimulatory effect of EGF.

Breast Neoplasms↗

Isoantigenic expression of Forssman glycolipid in human gastric and colonic mucosa: its possible identity with "A-like antigen" in human cancer.

The heterogenetic Forssman antigen is a glycosphingolipid, a ceramide pentasaccharide with the structure GalNAcalpha1-->3GalNAcbeta1-->3Galalpha1-->4Galbeta1-->4Glc-->ceramide. Forssman-positive animals are capable of synthesizing this compound in tissues or in erythrocytes, in contrast to the Forssman-negative species, including humans, which are incapable of adding the last carbohydrate in the sequence of the Forssman antigen, namely alphaGalNAc. The Forssman glycolipid and its precursor globoside were examined in twenty-one samples of surgically extirpated gastrointestinal mucosa and tumors derived therefrom. The results revealed that a few patients had chemically and immunologically detectable levels of the Forssman glycolipid as a normal component of their gastrointestinal mucosa (F(+) population); in contrast, the majority of patients did not contain this glycolipid in their normal mucosa (F(-) population). Whereas the F(-) population included blood groups A, B, and O, the F(+) population did not correspond to blood group A. The Forssman status in tumors taken from the F(+) or F(-) population showed the following striking features: (i) all tumors derived from F(-) mucosa possessed Forssman glycolipid, whereas (ii) none of the tumors originating in F(+) mucosa contained Forssman glycolipid. Globoside, the immediate precursor of Forssman antigen, was distributed equally among F(+) and F(-) mucosa and the tumors derived therefrom. Thus, the expression of Forssman antigen in gastrointestinal mucosa appears akin to that of an isoantigen. Furthermore, the Forssman antigen that appears in tumors of the F(-) population could represent a human tumor-associated antigen. In view of the strong crossreactivity of Forssman antigen with blood group A determinants, the appearance of Forssman antigen in human tumors could be related to the "A-like antigen" (or "neo-A antigen") of human tumors reported previously [Hakomori, S., Koscielak, J., Black, K. J. & Jeanloz, R. W. (1967) J. Immunol. 98, 31-38; Häkkinen, I. (1970) J. Natl. Cancer Inst. 44, 1183-1193].

ABO Blood-Group System↗

Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids.

Pneumonia is one of the most common causes of death from infectious disease in the United States. To examine the possible role of carbohydrates as adhesion receptors for infection, several pulmonary pathogenic bacteria were studied for binding to glycosphingolipids. Radiolabeled bacteria were layered on thin-layer chromatograms of separated glycosphingolipids, and bound bacteria were detected by autoradiography. The classic triad of infectious bacteria found in cystic fibrosis, Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus, along with other bacteria commonly implicated in typical pneumonia, such as Streptococcus pneumoniae, Klebsiella pneumoniae, and certain Escherichia coli, bind specifically to fucosylasialo-GM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Cer), asialo-GM1 (Gal beta 1-3GalNAc beta 1-4Gal beta-1-4Galc beta 1-1Cer), and asialo-GM2 (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer). Bacteria maintained in nutrient medium bind better than the same cells suspended in buffer. They do not bind to galactosylceramide, glucosylceramide, lactosylceramide, trihexosylceramide, globoside, paragloboside, Forssman glycosphingolipid, or several other glycosphingolipids tested, including the gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, and Cad. The finding that these pathogens do not bind to lactosylceramide suggests that beta 1-4-linked GalNAc, which is positioned internally in fucosylasialo-GM1 and asialo-GM1 and terminally in asialo-GM2, is required for binding. beta-N-Acetylgalactosamine itself, however, is not sufficient for binding, as the bacteria did not bind to globoside, which contains the terminal sequence GalNAc beta 1-3Gal. These data suggest that these bacteria require at least terminal or internal GalNAc beta 1-4Gal sequences unsubstituted with sialyl residues for binding. Other bacteria, including Mycoplasma pneumoniae, Streptococcus pyogenes, Salmonella species, and some E. coli, do not bind to the GalNAc beta 1-4Gal sequence. The biological relevance of these data is suggested by our finding that substantial amounts of asialo-GM1 occur in human lung tissue.

Animals↗

Structural relationships and sialylation among meningococcal L1, L8, and L3,7 lipooligosaccharide serotypes.

Eighteen of 34 endemic meningococcal case strains were of the L8 lipooligosaccharide (LOS) type; four of these were both L3 and L7 (L3,7), and seven were L1. L1 structures arose by alternative terminal Gal substitutions of lactosyl diheptoside L8 structures, as determined by electrospray ionization and other mass spectrometric techniques, and enzymatic and chemical degradations (Structures L1 and L1a). [see text for structure] The more abundant molecule, designated L1, had a trihexose globosyl alpha chain; the less abundant one, designated L1a, had a beta-lactosyl alpha chain and a parallel alpha-lactosaminyl gamma chain. A P(k) globoside (Galalpha1-->4Galbeta1-->4 Glc-R) monoclonal antibody bound 9/10 L1 strains, but a P(1) globoside (Galalpha1-->4Galbeta1-->4GlcNAc-R) mAb bound none of them. alpha-Galactosidase caused loss of both L1 structures and creation of L8 structures; beta-galactosidase caused loss of the L8 determinant. The L1/P(k) glycose was partially sialylated. Some LOS also had unsubstituted basal beta-GlcNAc additions. These structural relationships explain co-expression of L8, L1, and L3,7 serotypes.

Carbohydrate Conformation↗

Simian parvovirus infection: a potential zoonosis.

INTRODUCTION: Simian parvovirus (SPV) causes severe anemia in immunocompromised macaques. The closely related erythrovirus, parvovirus B19, causes anemia in susceptible humans and can be grown in human bone marrow mononuclear cells in vitro. We hypothesized that SPV may infect humans and replicate in human bone marrow mononuclear cells. METHODS: Serum samples from handlers of an SPV-seropositive macaque colony were tested by Western blot for evidence of antibodies to SPV. SPV capsid protein was expressed in insect cells, and SPV was cultured in human and macaque bone marrow mononuclear cells. RESULTS: Fifty-one percent of exposed handlers (n=65) were found to be SPV seropositive, compared with 35% of nonexposed individuals (n=124). In 17% of exposed handlers, compared with 6% of nonexposed individuals, antibodies were directed to SPV but not to B19. SPV capsid proteins, like those of B19, self-assembled to form parvovirus-like particles, and these capsids, like B19 capsids, bound to globoside, suggesting that globoside is also the receptor for SPV. We demonstrated that SPV could replicate in vitro in both human and macaque bone marrow mononuclear cells and that it was cytotoxic to erythroid progenitor cells. CONCLUSIONS: Our data suggest that SPV may infect human bone marrow mononuclear cells in vitro and in vivo and should be considered a potential zoonosis.

Animals↗

Long chain base and fatty acid compositions of equine kidney sphingolipids.

Equine renal glycopshingolipids were composed of galactocerebroside, glucocerbroside, ceramide dihexoside, ceramide trihexoside, sulfatide, globoside I, Forssman globoside, and hematoside. Free ceramide and sphingomyelin were also found in equine kidney. Their long chain bases consisted of sphingosine, dihydrosphingosine, C18-phytosphingosine, and C20-phytosphingosine, whereas the fatty acids were separated into two groups: nonhydroxy and hydroxy fatty acids. Ceramide monohexoside was separated into five spots by TLC on borax-impregnated plates. The major component of ceramide monohexoside was glucocerbroside which accounted for 46.6% of the total ceramide monohexoside and contained a ceramide consisting of phytosphingosines and hydroxy fatty acids. The long chain bases of hematoside and sulfatide contained dihydroxy and trihydroxy bases in nearly equal ratios. On the other hand, the other glycosphingolipids contained mainly dihydroxy bases, though with significant amounts of trihydroxy bases. Free ceramides were separated into four groups by silicic acid column chromatography and the major ceramides were of two kinds, consisting of dihydroxy bases and nonhydroxy fatty acids (49.9% of the total ceramide) and of trihydroxy bases and nonhydroxy fatty acids (38.5% of the total ceramide). The minor ceramides contained predominantly hydroxy fatty acids. Neither trihydroxy bases nor hydroxy fatty acids were detected in spingomyelin.

Animals↗

Liposome agglutination and liposomal membrane immune-damage assays for the characterization of antibodies to glycosphingolipids.

Antibodies against each of three neutral glycosphingolipids, Forssman glycolipid, globoside I, and asialo GM2, were elicited in rabbits. The specificity of these antibodies was studied by liposome agglutination and liposomal membrane immune-damage assays using liposomes prepared with each glycolipid hapten. Spectrophotometric measurement of liposome agglutination was found to be effective for detecting IgG antibodies, whereas complement-dependent immune-damage assay favored the expression of IgM antibodies. Three glycosphingolipids having the same non-reducing terminal N-acetylgalactosamine residues were discriminated with IgG antibodies, while IgM antibodies showed cross-reactivity. Specifically purified anti-Forssman and anti-asialo GM2 antibodies reacted only with Forssman glycolipid and asialo Gm2, respectively, but purified anti-globoside I antibodies cross-reacted with asialo GM2.

Agglutination↗

Structural requirements for the glycolipid receptor of human uropathogenic Escherichia coli.

The binding of uropathogenic Escherichia coli to the globo series of glycolipids via P pili is a critical step in the infectious process that is mediated by a human-specific PapG adhesin. Three classes of PapG adhesins exist with different binding specificities to Gal alpha 4Gal-containing glycolipids. The structural basis for PapG recognition of the human glycolipid receptor globoside was investigated by using soluble saccharide analogues as inhibitors of bacterial haemagglutination. The minimum binding epitope was confirmed as the Gal alpha 4Gal moiety, but parts of the GalNAc beta and glucose residues, which flank the Gal alpha 4Gal in globoside (GbO4), were also shown to be important for strong binding. Furthermore, the same five hydroxyl groups of Gal alpha 4Gal in globotriasyl ceramide that were recognized by a previously characterized PapG variant were also recognized by the human-specific PapG in binding the GbO4 that dominates in the human kidney. Saccharide analogues that blocked haemagglutination also blocked the adherence of human uropathogenic E. coli to human kidney sections. Knowledge of the molecular details of the PapG-GbO4 interaction will make it possible to design antiadherence therapeutics.

Adhesins, Escherichia coli↗

Complement fixation antibodies to glycosphingolipids in sera of rare blood group p and Pk phenotypes.

Blood group P antigen and Pk antigen were recently identified as glycosphingolipid globoside, GalNAc(beta, 1 leads to 3)Gal(alpha, 1 leads to 4)Gas(beta, 1 leads to 4)Glc(beta, 1 leads to 1)ceramide, and trihexosylceramide, Gal(alpha, 1 leads to 4)Gal(beta, 1 leads to 4)Gld(beta, 1 leads to 1)ceramide, respectively (Naiki & Marcus, 1974). The presence of antibodies to both antigens in the sera from rare p donors and antibodies to P antigen in the serum from a rare Pk donor were first demonstrated by the complement fixation test with the optimal antigen preparations containing each purified glycoplipid, lecithin and cholesterol. In the serum from a p donor, most of antibody population of anti-P was IgM and was cross-reacted to Forssman glycolipid, GalNAc(alpha, 1 leads to 3)GalNAc(beta, 1 leads to 3)Gal(alpha, 1 leads to 4)Gal(beta, 1 leads to 4)Glc(beta 1 leads to 1) ceramide, but the rest of the anti-P antibodies and most of anti-Pk antibodies were IgG and had marked specificities for globoside and trihexosylceramide, respectively.

Antibodies↗

Four new human renal cell carcinoma cell lines expressing globo-series gangliosides.

Clinicopathological studies revealed that monosialosyl galactosyl globoside (MSGG) and disialosyl galactosyl globoside (DSGG) expressed by renal cell carcinoma (RCC) are one of the biochemical indicator related to the metastatic potential. The present study examines the characteristics of four new human RCC cell lines and compares the expression of MSGG and DSGG among them using TLC immunostaining and flow cytometry. TOS-1 and TOS-2 were derived from metastatic subcutaneous tissues. TOS-3 and TOS-3LN were derived from the primary lesion and from metastatic lymph nodes respectively. Monolayer culture, light microscopy and electron microscopy of these cells showed that these cell lines were derived from RCC. TLC immunostaining and flow cytometric analysis revealed increased levels of MSGG in TOS-2 and TOS-3LN, and increased DSGG in TOS-1 and TOS-3LN. These cell lines would be useful for functional studies of globo-series ganglioside expressed by RCC.

Adenocarcinoma, Clear Cell↗

Glycosphingolipids in murine lymphocytes from thymus and spontaneous and X-ray induced thymomas.

Lymphocytes from spontaneous thymoma in AKR mice and from X-ray induced thymoma in C57B1/6 mice showed elevated levels (by 50% and 100%, respectively) of lipid-bound sialic acid as compared with lymphocytes from normal thymuses used as controls. Some ganglioside fractions in thymomas were elevated 4-6-fold over those in normal thymuses while other fractions decreased or disappeared. Neutral glycosphingolipid (NGSL) content in lymphocytes from thymomas was also changed. Thin-layer chromatography of NGSLs showed that the fractions migrating as ceramide monohexoside (CMH), dihexoside (CDH) and below globoside standards were increased, respectively, 2-3-fold, 3-6-fold and 2-fold in both types of thymomas. Methylation and gas-liquid chromatography analysis confirmed the presence of CMH, CDH and globoside in NGSLs isolated from X-ray induced thymoma.

Animals↗

Generalized accumulation of neutral glycosphingolipids with G M2 ganglioside accumulation in the brain.

Analyses have been made of glycosphingolipids from visceral organs and brain of a patient with an unusual lipid storage disorder diagnosed initially as classical Tay-Sachs disease. Levels of the lipids from fresh-frozen sections of gray and white matter, kidney, spleen, liver, and heart from this patient were compared with those of normal juvenile controls, and the fatty acid composition of accumulated glycosphingolipids was compared with reference compounds. This patient was found to have abnormally high concentrations of a globoside in liver, kidney, and spleen, asialo G(M2) ganglioside in brain and liver, and G(M2) ganglioside in the brain. On the basis of these findings along with the clinical manifestations of Tay-Sachs disease with visceral involvement (hepatosplenomegaly) and demonstration of total deficiency of both A and B components of beta-N-acetylhexosaminidase activity, this glycosphingolipidosis is the same as two previously reported cases of G(M2) gangliosidosis with globoside accumulation and total beta-N-acetylhexosaminidase deficiency.

Brain↗

Specific radioactive labeling of terminal n-acetylgalactosamine of glycosphingolipids by the galactose oxidase-sodium borohydride method.

The galactose oxidase-sodium borohydride method was used to specifically label the terminal N-acetylgalactosamine of three glycosphingolipids, Gm2-ganglioside, asialo-Gm2-ganglioside, and globoside. All of the compounds showed a minimum of 95% radiopurity, and generally more than 90% of the total radioactivity was located in the terminal galactosamine moiety. Globoside and asialo-Gm2-ganglioside were labeled to high specific activities comparable with those of the sphingolipids with a terminal galactose moiety, labeled with the same procedure. These labeled compounds were well suited as substrates for the study of specific sphingolipid N-acetylgalactosaminidase. Gm2-ganglioside, however, was a poor substrate for galactose oxidase, and its specific activity was only a small percentage of the others. Furthermore, because of the low specific activity of the galactosamine moiety, it was necessary to pretreat Gm2-ganglioside with unlabeled sodium borohydride to reduce the nonspecific labeling of other portions of the molecule. The use of labeled sodium borohydride of a very high specific activity may yield specifically labeled Gm2-ganglioside suitable for metabolic studies. Thus, the method is useful for labeling not only terminal galactose but also terminal N-acetylgalactosamine of glycosphingolipids.

Alcohol Oxidoreductases↗

Concentrations of glycosyl ceramides in plasma and red cells in Fabry's disease, a glycolipid lipidosis.

Concentrations of four neutral glycosyl ceramides were determined in plasma and erythrocytes from nine hemizygous patients with Fabry's disease (a hereditary glycolipid lipidosis), from the sister of one of the patients, and from the heterozygous mother of another one. The concentration of a trihexosyl ceramide, galactosylgalactosylglucosyl ceramide, was elevated in plasma from the patients about threefold above the normal mean level, and the amount of this lipid was also increased in plasma from the two female relatives. The concentrations of glucosyl ceramide and lactosyl ceramide in plasma were slightly less than normal in the affected males, while globoside or a similar tetrahexosyl ceramide was slightly higher than normal. All but one of the Fabry patients had significantly less globoside in the red cells, as compared with the normal range, although the red cell concentration of trihexosyl ceramide was normal in all of the patients. Thus the concentration of the lipid that accumulates in the tissues in Fabry's disease is elevated in plasma but not in red cells, whereas in Gaucher's disease the accumulating lipid (glucosyl ceramide) is elevated in both plasma and red cells.

Adolescent↗

Abnormality of serum lipoprotein and spleen glycosphingolipids in a case of hereditary spherocytosis.

A patient with hereditary spherocytosis gave rise to lower levels of both erythrocyte and serum cholesterols and serum lipoproteins than normal subjects. Abnormal shape of the serum lipoprotein particles was observed by electron-microscopic examination as well as the spheroidal shape of red cells. Lipids of fresh spleen tissue of the patient after splenectomy for the treatment of splenomegaly were extracted, isolated and analyzed. Particularly, different glycosphingolipids were also chemically identified and analyzed. The total lipids accounted for 10.7% of the dry tissue weight and consisted of cholesterol (32.2%), simple lipids (5.4%),phospholipids (58.3%) and glycosphingolipids (3.6%). Particularly, the glycosphingolipids were composed of monohexosyl ceramide (9.0%), lactosyl ceramide (31.2%), digalactosylglucosyl ceramide (9.2%), globoside I (27.6%) and hematoside (23.0%). It was found that the globoside I and hematoside increased remarkably in the spleen of patient with hereditary spherocytosis and that monohexosyl ceramide contained not only glucosyl ceramide, but also galactosyl ceramide at the ratio of 4:1.

Adult↗

Immunochemical observations on the human blood group P system.

Haemagglutination inhibition experiments were carried out with anti-P1, anti-Pk and anti-P sera in an attempt to increase understanding of the chemical, genetical and serological relationships within the P system. The test-substances comprised a glycoprotein with human blood group P1 and Pk activity isolated from sheep hydatid cyst fluid, fragments isolated from the partial acid hydrolysis products of the P1Pk active glycoprotein, glycolipids, monosaccharides and di- and oligo-saccharides of known structure. The trisaccharide alphaGal(1 leads to 4)betaGal(1 leads to 4)GlcNAc isolated from the glycoprotein hydrolysis products, and earlier established as the P1 determinant (Cory et al., 1974), was the only low molecular weight compound that gave strong inhibition with human, rabbit and goat anti-P1 sera. A disaccharide alphaGal(1 leads to 4)Gal, also isolated from the glycoprotein hydrolysis products, failed to react with anti-P1 reagents but inhibited human anti-Pk sera as strongly as the trisaccharide. The glycolipid alphaGal(1 leads to 4)betaGal(1 leads to 4)Glc-Cer (Ceramide trihexoside) and other oligosaccharides containing alphaGal(1 leads to 4)Gal at the non-reducing terminal were also strong inhibitors of anti-Pk sera. Oligosaccharides with terminal alpha-galactosyl residues joined in other positional linkages gave definite, although less strong, inhibition. The inhibition results suggest a close structural relationship between the P1 and Pk determinants and indicate that the specificity of anti-Pk sera is less closely delineated than that of anti-P1. Human anti-P sera differed markedly from anti-P1 and anti-Pk and were not inhibited by any of the compounds containing alpha-galactosyl residues. The glycolipid betaGalNAc(1 leads to 3)alphaGal(1 leads to 4)betaGal(1 leads to 4)Glc-Cer (globoside) strongly inhibited the anti-P sera. The inhibition of anti-Pk and anti-P sera by ceramide trihexoside and globoside, respectively, confirms the observations of Naiki & Marcus (1974) and supports their conclusions that Pk is the precursor of P. The genetic relationship of the P1 antigen to P and Pk is not clear but biosynthetic pathways are discussed that might explain the absence of P1, Pk and P antigens in individuals of the p phenotype.

Blood Group Antigens↗

Characterization of human sperm plasma membrane: glycolipids and polypeptides.

The plasma membranes from ejaculated human spermatozoa were removed by nitrogen cavitation (600 PSI for 10 min) and isolated by centrifugation followed by a discontinuous sucrose density gradient centrifugation. Glycolipid analysis of the plasma membrane revealed a three-fold enrichment in gangliosides: GM3 and GD1a/GD1b and neutral glycolipids: globoside and sulfatide as compared to that of whole human sperm. Two dimensional electrophoresis of human sperm plasma membranes revealed about 75 polypeptides. Several of these polypeptides were similar in migration and in display of shape and color to that found in boar sperm plasma membranes.

Cell Membrane↗

Recent advances in structural analysis of gangliosides: primary and secondary structures.

High-field (500 MHz) proton NMR has been used to elucidate the primary and secondary structures of glycosphingolipids (GSLs). Using 2-D J-correlated spectroscopy (2-D SECSY) which establishes scalar couplings of protons, the monosaccharide composition, anomeric configuration and aglycon structures of a GSL can be established. 2-D nuclear Overhauser effect spectroscopy (2-D NOE) then establishes through-space intra- and inter-residue couplings of cross-relaxing protons. We have found that each anomeric proton is involved in NOE couplings with inter- and intra-residue protons. The inter-residue coupling, resulting from interaction of protons across the glycosidic linkage, establishes the n-1 sugar residue and specific glycosidation site to which the n-residue is linked. When such information is known for each residue and is combined, the sequence of the core oligosaccharide is obtained. The sialylation-induced glycosidation shift is then used to establish the site of sialic acid residue attachment in a ganglioside molecule. We have also observed that the anomeric proton inter-residue NOE couplings can be used to suggest the preferred conformation of an oligosaccharide. We have found that the oligosaccharide residue of globoside exists in a unique and rather rigid conformation which could be stabilized by hydrogen bonds and van der Waals interactions. Since GSLs are known to have a receptor role and are implicated in cell-cell recognition, enzyme-substrate interaction and antigen-antibody interaction, the determination of their conformation should be useful in understanding their biological functions.

Animals↗