Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
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Showing 1-14 articles out of 14 articles from the selected issue
MINIREVIEW
  • Momoko Onda, Wataru Hakamata
    2018 Volume 30 Issue 176 Pages E139-E145
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS OPEN ACCESS

    Antivirals are used to treat viral infections, and antibiotics are used to treat bacterial infections. However, the mechanisms of action and number of commercially available antivirals are very limited compared to those for antibiotics. Accordingly, our group is engaged in ongoing research to develop host-targeting antivirals for the virus infections. This work is primarily focused on the endoplasmic reticulum (ER) glucosidases involved in N-glycan synthesis as the host-dependent factors of viral infection. It is widely accepted that a key mechanism by which those inhibitors act as antivirals is their ability to disrupt virus glycoprotein folding via their inhibition of ER glucosidases. Importantly, very few virus strains are resistant to ER glucosidase inhibitors because ER glucosidase enzymes are not encoded on virus genomes. This avoids problems arising from resistance mutations occurring in the viral target. A number of ER glucosidase inhibitors with antiviral activity have been reported in the past, and several clinical trials of these have been performed. In this paper, we examine the factors preventing the development of these inhibitors as antivirals and our attempts to overcome them.

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  • Tomomi Izumikawa, Naoki Itano
    2018 Volume 30 Issue 176 Pages E147-E154
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    Cancer stem cells (CSCs) are capable of self-renewal and give rise to a malignant progeny that drives cancer development and progression. They are also believed to be responsible for cancer recurrence due to their resistance to chemotherapy and radiotherapy. Thus, elucidating the molecular mechanisms that govern CSCs could lead to new strategies for targeting cancer progression and recurrence. Emerging evidence revealed the existence of cancer cell plasticity, allowing cells to dynamically revert to a CSC state. Metabolic reprogramming, particularly in carbohydrate metabolism, has been implicated in this cancer cell plasticity. We recently demonstrated that hyaluronan (HA) production plays a role in regulating metabolic programs and CSC-like properties of breast cancer cells. In this review, we present the current evidence on metabolic reprogramming driven by HA production in CSCs.

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  • Makoto Hirano
    2018 Volume 30 Issue 176 Pages E155-E160
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    Incorporating substances from outside across plasma membranes is an essential process for cells. Receptor-mediated endocytosis plays important roles for uptake and subsequent degradation and processing of nutrients and vitamins. Megalin is a multi-ligand endocytic receptor that contributes to absorption of low molecular weight proteins on the cell surface. Megalin is a 600 kDa single-spanning transmembrane glycoprotein. It has a large extracellular domain in the N-terminus that contains four ligand-binding regions. Megalin binds with functionally and structurally distinct proteins (e.g., vitamin-binding proteins, carrier proteins and hormones) and chemical drugs (e.g., aminoglycosides) as ligands. Through the uptake of ligands, megalin mediates physiological functions in the body. Although megalin is highly glycosylated and the glycan structures have been analyzed using mass spectrometry, little has been known about the function of glycan on megalin. This article introduces the function of endocytosis mediated by megalin under physiological and pathological conditions and the effects of glycosylation of megalin on ligand-binding activity as function of glycans.

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  • Hiroto Hirayama
    2018 Volume 30 Issue 176 Pages E161-E167
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    Glycosylation is a major form of co-/post-translational modification associated with a variety of biological processes. Research in the field of glycobiology has elucidated details of glycan biosynthesis pathways as well as the diverse functions of glycans in biological processes. The detailed mechanisms of lysosomal degradation/turnover of glycans and the correlation between dysfunction of lysosomal enzymes involved in glycan degradation and lysosomal storage diseases are also well described. “Free” forms of glycans, unconjugated oligosaccharides designated “free N-glycans” (fNGs), continuously accumulate and undergo degradation in the cytosol. However, details regarding several steps in fNGs generation and degradation pathways as well as the biological significance of fNGs turnover remain to be elucidated. This article summarizes recent findings and the current state of knowledge regarding the detailed mechanisms and physiologic role of fNGs metabolism and discusses the diversity of fNGs structures and degradation pathways in eukaryotes.

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GLYCODEBUT
  • Yuya Taguchi, Daisuke Fujinami, Daisuke Kohda
    2018 Volume 30 Issue 176 Pages E169-E174
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    The glycosylation on asparagine residues is one of the ubiquitous protein modifications occurring in the three domains of life. An oligosaccharide chain is preassembled on a lipid-phospho carrier, which is referred to as lipid-linked oligosaccharide (LLO), and transferred to asparagine residues in polypeptide chains by the action of a membrane-bound enzyme, oligosaccharyltransferase. The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol–diphosphate–oligosaccharide in Eukarya, and polyprenol–diphosphate–oligosaccharide in Eubacteria. The oligosaccharide donor of an archaeal species was reported as dolichol–monophosphate–oligosaccharide. Thus, the difference in the number of phosphate groups aroused interest in whether the use of the monophosphate type donor is widespread in the domain Archaea. In this study, we selected four archaeal species to widely sample the domain Archaea. We used normal-phase liquid chromatography to purify the LLO from cultured archaeal cells and performed ESI-MS analysis to determine the chemical structure of the lipid-phospho part. We found that two euryarchaeal oligosaccharide donors of more ancient origin were a dolichol-monophosphate type, whereas the two crenarchaeal oligosaccharide donors of closer origin to Eukarya were a dolichol–diphosphate type. The present comparative study provides a new insight into the evolution of the oligosaccharide donor in the N-glycosylation system.

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GLYCOTOPIC
MINIREVIEW (Jpn. Ed.)
  • Momoko Onda, Wataru Hakamata
    2018 Volume 30 Issue 176 Pages J115-J121
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS OPEN ACCESS

    Antivirals are used to treat viral infections, and antibiotics are used to treat bacterial infections. However, the mechanisms of action and number of commercially available antivirals are very limited compared to those for antibiotics. Accordingly, our group is engaged in ongoing research to develop host-targeting antivirals for the virus infections. This work is primarily focused on the endoplasmic reticulum (ER) glucosidases involved in N-glycan synthesis as the host-dependent factors of viral infection. It is widely accepted that a key mechanism by which those inhibitors act as antivirals is their ability to disrupt virus glycoprotein folding via their inhibition of ER glucosidases. Importantly, very few virus strains are resistant to ER glucosidase inhibitors because ER glucosidase enzymes are not encoded on virus genomes. This avoids problems arising from resistance mutations occurring in the viral target. A number of ER glucosidase inhibitors with antiviral activity have been reported in the past, and several clinical trials of these have been performed. In this paper, we examine the factors preventing the development of these inhibitors as antivirals and our attempts to overcome them.

    Download PDF (2473K)
  • Tomomi Izumikawa, Naoki Itano
    2018 Volume 30 Issue 176 Pages J123-J130
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    Cancer stem cells (CSCs) are capable of self-renewal and give rise to a malignant progeny that drives cancer development and progression. They are also believed to be responsible for cancer recurrence due to their resistance to chemotherapy and radiotherapy. Thus, elucidating the molecular mechanisms that govern CSCs could lead to new strategies for targeting cancer progression and recurrence. Emerging evidence revealed the existence of cancer cell plasticity, allowing cells to dynamically revert to a CSC state. Metabolic reprogramming, particularly in carbohydrate metabolism, has been implicated in this cancer cell plasticity. We recently demonstrated that hyaluronan (HA) production plays a role in regulating metabolic programs and CSC-like properties of breast cancer cells. In this review, we present the current evidence on metabolic reprogramming driven by HA production in CSCs.

    Download PDF (3598K)
  • Makoto Hirano
    2018 Volume 30 Issue 176 Pages J131-J136
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    Incorporating substances from outside across plasma membranes is an essential process for cells. Receptor-mediated endocytosis plays important roles for uptake and subsequent degradation and processing of nutrients and vitamins. Megalin is a multi-ligand endocytic receptor that contributes to absorption of low molecular weight proteins on the cell surface. Megalin is a 600 kDa single-spanning transmembrane glycoprotein. It has a large extracellular domain in the N-terminus that contains four ligand-binding regions. Megalin binds with functionally and structurally distinct proteins (e.g., vitamin-binding proteins, carrier proteins and hormones) and chemical drugs (e.g., aminoglycosides) as ligands. Through the uptake of ligands, megalin mediates physiological functions in the body. Although megalin is highly glycosylated and the glycan structures have been analyzed using mass spectrometry, little has been known about the function of glycan on megalin. This article introduces the function of endocytosis mediated by megalin under physiological and pathological conditions and the effects of glycosylation of megalin on ligand-binding activity as function of glycans.

    Download PDF (2567K)
  • Hiroto Hirayama
    2018 Volume 30 Issue 176 Pages J137-J143
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    Glycosylation is a major form of co-/post-translational modification associated with a variety of biological processes. Research in the field of glycobiology has elucidated details of glycan biosynthesis pathways as well as the diverse functions of glycans in biological processes. The detailed mechanisms of lysosomal degradation/turnover of glycans and the correlation between dysfunction of lysosomal enzymes involved in glycan degradation and lysosomal storage diseases are also well described. “Free” forms of glycans, unconjugated oligosaccharides designated “free N-glycans” (fNGs), continuously accumulate and undergo degradation in the cytosol. However, details regarding several steps in fNGs generation and degradation pathways as well as the biological significance of fNGs turnover remain to be elucidated. This article summarizes recent findings and the current state of knowledge regarding the detailed mechanisms and physiologic role of fNGs metabolism and discusses the diversity of fNGs structures and degradation pathways in eukaryotes.

    Download PDF (1927K)
GLYCODEBUT (Jpn. Ed.)
  • Yuya Taguchi, Daisuke Fujinami, Daisuke Kohda
    2018 Volume 30 Issue 176 Pages J145-J150
    Published: September 25, 2018
    Released: September 25, 2018
    JOURNALS RESTRICTED ACCESS

    The glycosylation on asparagine residues is one of the ubiquitous protein modifications occurring in the three domains of life. An oligosaccharide chain is preassembled on a lipid-phospho carrier, which is referred to as lipid-linked oligosaccharide (LLO), and transferred to asparagine residues in polypeptide chains by the action of a membrane-bound enzyme, oligosaccharyltransferase. The oligosaccharide donor for the oligosaccharyl transfer reaction is dolichol–diphosphate–oligosaccharide in Eukarya, and polyprenol–diphosphate–oligosaccharide in Eubacteria. The oligosaccharide donor of an archaeal species was reported as dolichol–monophosphate–oligosaccharide. Thus, the difference in the number of phosphate groups aroused interest in whether the use of the monophosphate type donor is widespread in the domain Archaea. In this study, we selected four archaeal species to widely sample the domain Archaea. We used normal-phase liquid chromatography to purify the LLO from cultured archaeal cells and performed ESI-MS analysis to determine the chemical structure of the lipid-phospho part. We found that two euryarchaeal oligosaccharide donors of more ancient origin were a dolichol-monophosphate type, whereas the two crenarchaeal oligosaccharide donors of closer origin to Eukarya were a dolichol–diphosphate type. The present comparative study provides a new insight into the evolution of the oligosaccharide donor in the N-glycosylation system.

    Download PDF (2205K)
GLYCOTOPIC (Jpn. Ed.)
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