Sugar Chains Of Glycoconjugates Research Articles

Structures and application of oligosaccharides in human milk

Comparative study of the oligosaccharide profiles of individual human milk revealed the presence of three different patterns. Four oligosaccharides containing the Fucα1-2Gal group were missing in the milk of non-secretor, and three oligosaccharides containing the Fucα1-4GlcNAc group were missing in the milk of Lewis negative individuals. Disappearance of some major oligosaccharides in these samples led to the finding of five novel minor oligosaccharides, which were hidden under the missing oligosaccharides. Following these studies, structures of many novel milk oligosaccharides were elucidated. At least 13 core oligosaccharides were found in these oligosaccharides. By adding α-fucosyl residues and sialic acid residues to these core oligosaccharides, more than one hundred oligosaccharides were formed. All these oligosaccharides contain lactose at their reducing termini. This evidence, together with the deletion phenomena found in the milk oligosaccharides of non-secretor and Lewis negative individuals, suggested that the oligosaccharides are formed from lactose by the concerted action of glycosyltransferases, which are responsible for elongation and branching of the Galβ1-4GlcNAc group in the sugar chains of glycoconjugates on the surface of epithelial cells. Therefore, oligosaccharides in human milk could include many structures, starting from the Galβ1-4GlcNAc group in the sugar chains of various glycoconjugates. Many lines of evidence recently indicated that virulent enteric bacteria and viruses start their infection by binding to particular sugar chains of glycoconjugates on the target cell surfaces. Therefore, milk oligosaccharides could be useful for developing drugs, which inhibit the infection of bacteria and viruses.

Soyasaponin I decreases the expression of α2,3-linked sialic acid on the cell surface and suppresses the metastatic potential of B16F10 melanoma cells

The transfer of sialic acids to the non-reducing terminal positions on sugar chains of glycoconjugates is catalyzed by sialyltransferases (STs). Increased sialylation is correlated with oncogenic transformation and metastatic potential. ST inhibitors may be potentially valuable as anti-cancer and anti-metastatic agents. In this study, we evaluated the effects of soyasaponin I (Ssa I), a known inhibitor of STs, on tumor metastasis through studying a highly metastatic cancer cell line B16F10. Ssa I specifically inhibited the expression of α2,3-linked sialic acids without affecting other glycans on the B16F10 cell surface. We also found that Ssa I decreased the migratory ability of cells, enhanced cell adhesion to extracellular matrix proteins. Finally, a pulmonary metastasis assay demonstrated that alteration of glycosylation in this way significantly reduced the ability of tumor cells to distribute to the lungs of mice. Collectively, these findings suggested that α2,3-linked sialic acids may play an important role in metastasis potential of B16F10 cells.

Glycobiology in the field of aging research—introduction to glycogerontology

In populations where demographies are shifting towards increased average age, the importance of gerontology is also increasing. The main purpose of gerontology is to elucidate the mechanisms of deterioration, which occur in various parts of the human body through aging, and use this knowledge to improve quality of life among the elderly. By the elucidation of the human genome, a revolutionary development is expected to occur in the field of medical science in the near future. Many important genes related to the aging processes of various organs have already been found and are expected to be useful in the future development of geriatric medicine. However, most of the proteins produced by the human body contain sugar chains, whose importance as biosignals for multi-cellular organisms was revealed by the recent development of the new field of glycobiology. Since sugar chains are formed as secondary gene products by the concerted action of glycosyltransferases, the structures of sugar chains are less strictly regulated than proteins. Accordingly, most of the biosignals associated with sugar chains are not essential for the maintenance of life itself, but are necessary to maintain the ordered social life of cells constructing multi-cellular organisms. Hence, investigation of structural changes of sugar chains that is caused by aging is expected to produce quite a lot of useful information pertaining to the elucidation of diseases induced by aging. This review will summarize our current knowledge of such changes found in the sugar chains of glycoconjugates resulting from the aging process.

Combination Assay of Urinary Free l -fucose and Trypsin Inhibitor may be Useful Indicators of Disease Activity in Patients with Hematologic Malignancies

l -Fucose is a monosaccharide located at the non-reducing ends of sugar chains of glycoconjugates. Urinary l -fucose (U-FC) is excreted as free l -fucose, and clinically useful as a tumor marker of digestive organ cancers. We evaluated the clinical usefulness of U-FC levels in patients with various hematologic malignancies because U-FC for hematologic malignancies has only rarely been described. The mean U-FC levels in the acute nonlymphocytic leukemia (ANLL), myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) groups were significantly higher than in the control group (P <0.05). Recently, we reported that urinary trypsin inhibitor (UTI) levels in patients with ANLL, MDS, non-Hodgkin's lymphoma and multiple myeloma were significantly elevated, compared with those in healthy adult volunteers. Noninvasive combination assays of UTI and U-FC may have a higher accuracy in diagnosis of ANLL and MDS than those of UTI or U-FC alone. UTI and U-FC combination assays, noninvasive for patients, could be expanded as useful indicators in hematologic malignancies.

The history of glycobiology in Japan

This mini review surveys the major accomplishments in the field of glycoconjugates research in Japan, which were made after World War II. It describes early movements in the field of glycoconjugate research in Japan, development of the new techniques to investigate structures of the sugar chains of glycoconjugates, studies of the functions of the sugar chain moieties, and the political movement in Japan to support the basic research necessary for the development of glycotechnology. As introduced in this short article, important groundwork for glycobiology was made by Japanese researchers.

Lectin-histochemical analysis of pleomorphic adenoma of the lacrimal gland

The sugar structures of the glycoconjugates in pleomorphic adenoma of the lacrimal gland were analyzed by examining the binding sites of 5 biotinylated lectins on tissue sections with or without sialidase digestion. Both galactose (Gal) beta 1,3 N-acetylgalactosamine and Gal beta 1,4 N-acetylglucosamine were present on the surfaces of ductal basal cells and stromal cells. The galactsyl residues in the glycoconjugates of ductal basal cells were either sialylated or exposed, whereas those of stromal cells were all sialylated. Since the synthesis of sugar chains of glycoconjugates is terminated by sialylation, their structure may mature as they progress from ductal basal cells to stromal cells.

Immunological detection of the fungal parasite, Pythium sp.; the causative organism of red rot disease in Porphyra yezoensis

The red rot disease of Porphyra yezoensis Ueda (Rhodophyta) is caused by a parasitic fungus, Pythium sp. To facilitate the detection of this pathogen in infected thalli of P. yezoensis, polyclonal and monoclonal antibodies were prepared. Antibodies were raised against antigen prepared from an isolate of fungal hyphae obtained from red-rot infected thallus of P. yezoensis from Aichi Prefecture. Polyclonal antibody was obtained from the antisera of immunized rabbits. Monoclonal antibody was obtained from the culture supernatant of a hybridoma which had been established by cell fusion between a myeloma cell line and spleen cells of immunized mice. Hyphae were detected by means of indirect fluorescent antibody technique. Titers of polyclonal antibodies obtained were too low to recognize fungal hyphae that had penetrated the thalli of P. yezoensis; however, monoclonal antibody was useful for the detection of fungi that had penetrated algal thalli. The monoclonal antibody was specific for the Pythium sp. from red-rot infected thalli of P. yezoensis from Saga (western Japan) and from Aichi Prefectures (central Japan), but was ineffective for infections from Miyagi Prefecture (northern Japan). It is evident, therefore, that Pythium sp. can give rise to immunologically distinct groups of red rot disease. Based on chemical and enzymatic treatments, the antigenic determinant appeared to localize on the sugar chains of glycoconjugates or the polysaccharides of the hyphal cell wall.

Metabolic Radiolabeling of Animal Cell Glycoconjugates

This unit describes metabolic labeling techniques that provide specific information about the structure, sequence, and distribution of the sugar chains of glycoconjugates. In the Basic Protocol, cells in culture are grown through several population doublings in complete medium supplemented with radiolabeled glycoconjugate precursors to reach a steady-state level of incorporation. In the alternate protocols, cells are cultured for a short period of time in a deficient medium that contains a high concentration of radiolabeled precursor. A pulse or pulse-chase labeling procedure is provided to analyze precursor-product relationships. With the sequential pulse-labeling method described here, it is possible to obtain quantities of labeled glycoconjugates with the use of a minimum amount of labeled precursor by using the same batch of medium to pulse-label a series of cultures. A support protocol describes the preparation of multiply deficient medium (MDM) for use in making appropriate deficient media.