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Molecular-patholical Analysis for the Biolocical Role of Ryudocan (Endothilal Heparan Sulfate Proteoglycan) on Vasculat Damage.

Research Project

Project/Area Number 06836009
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 血管生物学
Research InstitutionNagoya University

Principal Investigator

KOJIMA Tetsuhito  Nagoya Univ.Sch.Med.Assist.Prof., 医学部, 助手 (40161913)

Co-Investigator(Kenkyū-buntansha) ABE Akihiro  Nagoya Univ.Sch.Med.Clin.Staff, 医学部, 医員
安部 明宏  名古屋大学, 医学部, 医員
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsRyudocan / Heparan Sulfate / Proteoglycan / Immuno-histochemistry / bFGF / midkine / TFPI / Tisssue Factor Pathway Inhibitor (TFPI) / ミッドカイン(MK) / Tissue Factor Pathway Inhibitor(TFPI) / Inhibition radioimmuno-assay
Research Abstract

Ryudocan, a heparan sulfate proteoglycan, was isolated from human endothelial-like EAhy926 cells by the combination of ion-exchange and immuno-affinity chromatographies. Purified human ryudocan had biochemical properties similar to those of rat ryudocan isolated from microvascular endothelial cells. Human ryudocan contained only heparan sulfate (HS) glycosaminoglycan chains along with a core protein having an apparent molecular mass of 30 kDa. We evaluated the interactions between purified human ryudocan and several extracellular ligands by using a solid-phase binding assay. It was found that basic fibroblast growth factor (bFGF), midkine (MK), and tissue factor pathway inhibitor (TFPI) exhibited significant ryudocan binding. Heparitinase, but not chondroitin ABC lyase treatment, destroyed the ability of ryudocan binding to bFGF,MK,and TFPI.Heparin and HS,but not chondroitin surfate, inhibited such ryudocan binding. Thus, the HS chains of ryudocan appear to be responsible for its binding to bFGF,MK,and TFPI.The apparent dissociation constants for purified ryudokan were bFGF,0.50 nM ; MK,0.30 nM ; and TFPI,0.74 nM.Immunohistochemical analysis revealed that ryudocan was expressed in peripheral nerve tissues, fibrous connective tissues, and placental trophoblasts. These findings suggest that ryudocan may possess multiple biologic functions, such as bFGF modulation, neurite growth promotin, and anticoagulation, via HS-binding effectors in the cellular microenvironment.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] T.Kojima et al.: "Impaeired human fissue facior-mediated activity in blood clotting factor VII Nagoya (Arg 304→Try)." J.Biol.Chem.269. 7355-7363 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kojima et al.: "Establishment and Characterization of an Immature Human Megakavyoblastic Cell Line,MEG-A2" Leukemia. 9. 341-349 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kojima et al.: "A Quantitative Protein S Deficiency Associated with a Novel Neusense Mutation and Markedly Reduceed Levcls of Mutated mRNA." Thromb.Haemost.74. 590-595 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kojima et al.: "Ryudocan,Its Moleculav Structure and Function." Trends in Glycosci.Glycotech.7. 385-403 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kojima et al.: "Diagnosis of Hemophilia B Carriers Using Two Novel Dinucleotide Polymorphisms and Hha I RFLP of the Factor IX Gene in Japanese Subjects" Thromb Haemost. 74. 1009-1014 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 小嶋哲人 他: "第VIII因子遺伝子逆位解析の重症血友病Aにおける保因者診断、出生前診断への応用" 臨床血液. 36. 1252-1256 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kojima et al.: "Factor XII, Prekallikrein,and high-molecular-weight kininogen.,in K.A.High and H.R.Roberts(ed):Molecular Basis of Thrombosis and Homostasis" New York,Mercel Dekker, 670 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "Impaired human tissue factor-mediated activity in blood clotting factor VIINagoya (Arg304->Try)." J.Biol.Chem.269. 7355-7363 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "Factor XII,prekallilrein, and highmolecular-weight kininogen., in K.A.High and H.R.Roberts (ed) : Molecular basis of thrombosis and Hemostasis." New York, Marcel Dekker. 269-285 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "Establishment and Characterization of an Immature Human Megakaryoblastic Cell Line, MEG-A2." Leukemia. 341-349 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "A.Quantitative Protein S Deficiency Associated with a Novel Nonsense Multation and Markedly Reduced Levels of Mutated mRNA." Thromb.Haemost. 74(2). 590-595 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "Ryudocan, Its Molecular Structure and Function." Trends in Glycosci.Glycotech.7. 385-403 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "Diagnosis of Hemophilia B Carriers Using Two Novel Dinucleotide Polymorphisms and Hha I RFLP of the Factor IX Gene in Japanese Subjects." Thromb.Haemost. 74(4). 1009-1014 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuhito Kojima, et al.: "Human Ryudocan from Endothelial-like Cells binds Basic Fibroblast Growth Factor, Midkine, and Tissue Factor Pathway Inhibitor." J.Biol.Chem.(in press.). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Kojima et al.: "Eotablishmant and Chanicteigation of an Immature Humas Migakaryoblastic cell Line,MEG-A2:" Leu Kecmia. 9. 341-349 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Kojima et al.: "A Quantitatiue Protein S Deficiency Associated with a Novel Nonscuse Mutation and Murkedly Reduwi Levels of Mutated mRNA" Thromb Haemost.74. 590-595 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Kojima et al.: "Ryudocan,Its Molecular Structure and Function" Treuds in Glycosci Glycotecb.7. 385-403 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Kojima et al.: "Diagnosis of Henopilia B Carriers Using Two Novcl Dinuelectide Polymo-phisins and Hha I RFLP of the Factor IX Gene in Japanese Subjects" Thromb Haemost. 74. 1009-1014 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小嶋哲人 他: "ヒト血管内皮ヘパラン硫酸プロチオグリカン-Ryudocanのコア蛋白cDNAクローニングおよび生物学的機能解析" 腎臓. 17. 41-42 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小嶋哲人 他: "第VIII因子遺伝子逆位解析の重症血友病Aにおける保因者診断出生前診断への応用" 臨床血液. 36. 1252-1256 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Kojima et al.: "Factor XII,Prekallikrein,and Higb,mole calan-weight kiuinogen.,in K.A.Higd and H.R.Robevls(ea):Molecolor Basis of Thrombosis and Himostasis" New Yosk,Mervel Dekker, 670 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Kojima et al.: "Impaired human tissue factor-mediated activity in blood cfotling factor VII Nagoya (Arg 304→Trp)" J.B.C.269. 7355-7363 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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