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2000 Fiscal Year Final Research Report Summary

神経突起伸長と血管新生におけるグリコサミノグリカン糖鎖の分子認識

Research Project

Project/Area Number 09470509
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKOBE PHARMACEUTICAL UNIVERSITY

Principal Investigator

SUGAHARA Kazuyuki  Dept.of Biochemistry, KOBE PHARMACEUTICAL UNIVERSITY Professor, 薬学部, 教授 (60154449)

Co-Investigator(Kenkyū-buntansha) YAMADA Shuhei  Dept.of Biochemistry, KOBE PHARMACEUTICAL UNIVERSITY Lecturer, 薬学部, 講師 (70240017)
KITAGAWA Hiroshi  Dept.of Biochemistry, KOBE PHARMACEUTICAL UNIVERSITY Assistant Professor, 薬学部, 助教授 (40221915)
Project Period (FY) 1997 – 2000
Keywordschondroitin sulfate / glycosaminoglycan / heparan sulfate / tumor suppressor / EXT gene family / neurite outgrowth / angiogenesis / glycosyltransferase
Research Abstract

1) The so-called D disaccharide unit was demonstrated in the chondroitin sulfate preparation purified from neonatal mouse brains. Neurite outgrowth promoting activity was also demonstrated for the commercial shark cartilage chondroitin sulfate D preparation which contained a high proportion of the D disaccharide unit.
2) It was demonstrated that the commercial squid cartilage chondroitin sulfate E preparation had neurite outgrowth promoting activity toward cultured neuronal cells derived from embryonic rat brains. The chondroitin sulfate E preparation was further demonstrated to bind midkine and inhibit the midkine-mediated neuronal cell adhesion to the culture substrate.
3) The tumor-derived adhesion factor, angiomodulin, promotes the cord formation towards the cultured human tumor cell line ECV304, and has been proposed to be associated with tumor angiogenesis. The angiomodulin-binding domain on heparan sulfate chains was shown to be larger than dodecasaccharides and highly sulfated.
4) Sulfation of the chondroitin sulfate chains and sulfotransferase activities in embryonic chick brains were shown to be regulated during embryonic development and neonatal growth.
5) Glucuronyltransferase that is involved in the synthesis of the glycosaminoglycan-protein linkage region tetrasaccharide sequence, GlcA-Gal-Gal-Xyl, was molecularly cloned and its properties were characterized.
6) A truncated tetrasaccharide fragment, GlcA-Gal-Gal-Xyl, which corresponded to the glycosaminoglycan-protein linkage region, was demonstrated on a part-time proteoglycan, α-thrombomodulin.
7) α-GalNAc transferase purified from the culture medium of a human sarcoma cell line was shown to be identical with the EXTL2 protein encoded by the EXTL2 gene, which belonged to the tumor suppressor EXT gene family, and to harbor the α-GlcNAc transferase activity that initiates and determines the heparan sulfate synthesis.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 北川裕之: "Developmental regulation of the sulfation profile of chondroitin sulfate chains in the chicken embryo brain"J.Biol.Chem.. 272(50). 31377-31381 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 灘中里美: "Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with neurite outgrowth promoting activity"J.Biol.Chem.. 273(6). 3296-3307 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川裕之: "Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycasns"J.Biol.Chem.. 273(12). 6615-6618 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山根ゆかり: "Molecular characterization of Xenopus embryo heparan sulfate : differential structural requirements for the specific binding to basic fibroblast growth factor and follistatin"J.Biol.Chem.. 273(13). 7375-7381 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Clement Albrecht: "The DSD-1-epitope depends on sulfation, correlates with chondroitin sulfate D motifs, and is sufficient to promote neurite outgrowth"J.Biol.Chem.. 273(43). 28444-28453 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 灘中里美: "Demonstration of the immature glycosaminoglycan tetrasaccharide sequence GlcAβ1-3Galβ1-3Galβ1-4Xylon recombinant soluble human α-thrombomodulin. A possible mechanism generating "part-time" proteoglycans"J.Biol.Chem.. 273(50). 33728-33734 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川裕之: "The tumor suppressor EXT-like gene EXTL2 encodes an α1,4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate"J.Biol.Chem.. 274(20). 13933-13937 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 灘中里美: "Involvement of the core protein in the first β-N-acetylgalactosamine transfer to the glycosaminoglycan-protein linkage region tetrasaccharide and in the subsequent polymerization : the critical determining step for chondroitin sulfate biosynthesis"Biochem.J.. 340(2). 353-357 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川裕之: "Identification and characterization of a novel UDP-GalNAc : GlcA β-R α1, 4-N-acetylgalactosaminyltransferase from a human sarcoma cell line"Glycobiology. 9(7). 697-703 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Clement Albrecht: "Chondroitin sulfatae E promoyes neurite outgrowth of embryonic day 18 hippocampal neurons"Neuroscience Lett.. 269(3). 125-128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 刀禰裕子: "Characterization of recombinant glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans"FEBS Lett.. 459(3). 415-420 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岸部順子: "Structural requirements of heparan slufate for the binding to the tumor-derived adhesion factor/angiomodulin that induces cord-like structures to ECV-304 human carcinoma cells"J.Biol.Chem.. 275(20). 15321-15329 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅原一幸: "Structure and function of oversulfated chondroitin sulfate variants : unique sulfation patterns andneuroregulatory activities"Trends Glycosci.Glycotechnol.. 12(67). 321-349 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 植岡千香子: "Neuronal cell adhesion, mediated by the heparin-binding neuroregulatory factor midkine, is specifically inhibited by chondroitin sulfate E"J.Biol.Chem.. 275(48). 37407-37413 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitagawa, Hiroshi: "Developmental regulation of the sulfation profile of chondroitin sulfate chains in the chicken embryo brain"J.Biol.Chem.. 272(50). 31377-31381 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nadanaka, Satomi: "Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with neurite outgrowth promoting activity"J.Biol.Chem.. 273(6). 3296-3307 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, Hiroshi: "Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycasns"J.Biol.Chem.. 273(12). 6615-6618 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ymane, Yukari: "Molecular characterization of Xenopus embryo heparan sulfate : differential structural requirements for the specific binding to basic fibroblast growth factor and follistatin"J.Biol.Chem.. 273(13). 7375-7381 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Clement, Albrecht: "The DSD-1-epitope depends on sulfation, correlates with chondroitin sulfate D motifs, and is sufficient to promote neurite outgrowth"J.Biol.Chem.. 273(43). 28444-28453 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nadanaka, Satomi: "Demonstration of the immature glycosaminoglycan tetrasaccharide sequence GlcAβ1-3Galβ1-3Galβ1-4Xyl on recombinant soluble human α-thrombomodulin. A possible mechanism generating "part-time" proteoglycans"J.Biol.Chem.. 273(50). 33728-33734 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, Hiroshi: "The tumor suppressor EXT-like gene EXTL2 encodes an α1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate"J.Biol.Chem.. 274(20). 13933-13937 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nadanaka, Satomi: "Involvement of the core protein in the first β-N-acetylgalactosamine transfer to the glycosaminoglycan-protein linkage region tetrasaccharide and in the subsequent polymerization : the critical determining step for chondroitin sulfate biosynthesis"Biochem.J.. 340(2). 353-357 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, Hiroshi: "Identification and characterization of a novel UDP-GalNAc : GlcA β-R α1, 4-N-acetylgalactosaminyltransferase from a human sarcoma cell line"Glycobiology. 9(7). 697-703 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Clement, Albrecht: "Chondroitin sulfatae E promoyes neurite outgrowth of embryonic day 18 hippocampal neurons"Neuroscience Letters. 269(3). 125-128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tone, Yuko: "Characterization of recombinant glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans"FEBS Letters. 459(3). 415-420 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishibe, Junko: "Structural requirements of heparan slufate for the binding to the tumor-derived adhesion factor/angiomodulin that induces cord-like structures to ECV-304 human carcinoma cells"J.Biol.Chem.. 275(20). 15321-15329 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugahara, Kazuyuki: "Structure and function of oversulfated chondroitin sulfate variants : unique sulfation patterns andneuroregulatory activities"Trends Glycosci.Glycotechnol.. 12(67), 12(67). 321-349 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueoka, Chikako: "Neuronal cell adhesion, mediated by the heparin-binding neuroregulatory factor nidkine, is specifically inhibited by chondroitin sulfate E"J.Biol.Chem.. 275(48). 37407-37417 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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