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Studies on the physiological function of sugar chains and the activation mechanism of human von Willebrand factor

Research Project

Project/Area Number 09671139
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionFujita Health University

Principal Investigator

MATSUI Taei  Fujita Health U.Inst.Comprehensive Med.Sci., Associate Prof., 総合医科学研究所, 講師 (90183946)

Co-Investigator(Kenkyū-buntansha) TITANI Koiti  Fujita Health U.Inst.Comprehensive Med.Sci., Prof., 総合医科学研究所, 教授 (60179942)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsvon Willebrand factor / blood group antigen / bone marrow transplantation / platelet / snake venom / protease / amino acid sequence / lectin / ABO血液型 / cDNA / メタロプロテアーゼ / ビチセチン / 一次構造 / ELISA / セリンプロテアーゼ / ブラジキニン
Research Abstract

1. The complete amino acid sequence of bitiscetin, a novel von. Willebrand factor (vWF) modulator protein from Bitis arietans snake venom, was determined. Bitiscetin was composed of disulfidelinked heterodimer of alpha and beta subunits. Both the subunits showed a C-type lectin motif and only 45% similarity to another modulator, botrocetin. The competition study suggests that bitiscetin binds to a site in the A1 domain of vWF located closely to the botrocetin-binding site.
2. ABO blood group antigen expression on plasma vWF of the patients who received ABO-mismatched bone marrow transplantation was monitored. Blood group antigens on the red blood cells gradually turned to the donor's type, but the antigens on the vWF still maintained the original recipient's type even after several years. The same results were obtained in the case of ABO-mismatched peripheral blood and cord blood stem cell transplantation.
3. A novel vWF-binding and -cleaving metalloproteinase named kaouthiagin was purified from Naja kaouthia cobra venom. Kaouthiagin specifically cleaved vWF between Pro-708 and Asp-709 to diminish the multimeric structure of vWF, resulting in the loss of ristocetin-induced platelet aggregability and collagen-binding activity of vWF.
4. A novel platelet GPIb-binding protein named mamushigin was purified from A.blomhoffii snake venom and the cDNA of mamushigin was cloned.
5. A novel fibrinogen-cleaving serine protease named halystase was purified from the snake venom of Agkistrodon halys blomhoffii and the complete amino acid sequence of halystase was determined. Halystase also cleaved plasma kininogen to produce bradykinin, causing the hypotension in rat.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] T.Matsui, et al.: "Complete amino acid sequence of bitiscetin, a novel von Willebrand factor modulator protein, purified from snake venom of Bitis arietans." Res.Commun.Biochem.Cell Mol.Biol.1. 271-284 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Kaouthiagin, a metalloproteinase purified from Naja kaouthia cobra venom, specifically binds to and cleaves von Willebrand factor." Blood. 90. 466a(abs) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Miura, et al.: "Dimeric structure of von Willebrand factor A1-loop region is required to show a complete inhibition on high-shear stress induced platelet aggregation." Blood. 90. 466a(abs) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Ozeki, et al.: "D-Galactoside-specific lectins from the body wall of an echiuroid(Urechis unicinctus)and two annelids(Neanthes japonica and Marphysa sanguinea)." Comp.Biochem.Physiol.118B. 1-6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Uchiyama, et al.: "Distribution and localization of galectin purified from Rana catesbeiana oocytes." Glycobiology. 7. 1159-1165 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Purification and amino acid sequence of halystase from snake venom of Agkistrodon halys blomhoffii, a serine protease specifically cleaving fibrinogen and kininogen." Eur.J.Biochem.252. 569-575 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Sakurai, et al.: "The cDNA cloning and molecular characterization of a snake venom platelet glyco-protein lb-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom." Thromb.Haemost.79. 1199-1207 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Hamako, et al.: "Purification and characterization of kaouthiagin, a von Willebrand factor-binding and cleaving metalloproteinase from Naja kaouthia cobra venom." Thromb.Haemost.80. 499-505 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 松井太衛: "「関西血栓フォーラム・血小板血栓形成の分子機構」藤村吉博 編" ライフサイエンス出版, 158-163 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 千谷晃一、他: "「関西血栓フォーラム・血小板血栓形成の分子機構」藤村吉博 編" ライフサイエンス出版, 182-189 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui and K.Titani.: "Methods in Mol.Medicine, Vol.9“Lectin Methods and Protocols", eds by J M Bhodes and J D Milton" Humana Press Inc., 235-245 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 松井太衛: "別冊 医学のあゆみ「血液疾患-state of arts」Ver.2坂田、平井、溝口 編" 医歯薬出版, 183-186 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Complete amino acid sequence of bitiscetin, a novel von Willebrand factor modulator protein, purified from snake venom of Bitis arietans." Res.Commun.Biochem.Cell Mol.Biol.1. 271-284 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Kaouthiagin, a metalloproteinase purified from Naja kaouthia cobra venom, specifically binds to and cleaves von Willebrand factor." Blood. 90 (abs). 466a (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Miura, et al.: "Dimeric structure of von Willebrand factor A1-loop region is required to show a complete inhibition on high-shere stress induced platelet aggregation." Blood. 90 (abs). 466a (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Ozeki, et al.: "D-Galactoside-specific lectins from the body wall of an echiuroid (Urechis unicinctus) and two annelids (Neanthes japonica and Marphysa sanguinea)." Comp.Biochem.Physiol.118B. 1-6 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Uchiyama, et al.: "Distribution and localization of galectin purified from Rana catesbeiana oocytes." Glycobiology. 7. 1159-1165 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui, et al.: "Purification and amino acid sequence of halystase from snake venom of Agkistrodon halys blomhoffii, a serine protease specifically cleaving fibrinogen and kininogen." Eur.J.Biochem.252. 569-575 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Sakurai, et al.: "The cDNA cloning and molecular charac-terization of a snake venom platelet glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom." Thromb.Haemost.79. 1199-1207 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Hamako, et al.: "Purification and characterization of kaou-thiagin, a von Willebrand factor-binding and cleaving metalloproteinase from Naja kaouthia cobra venom." Thromb.Haemost. 80. 505 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsui and K.Titani.: ABO (H) blood group expression on circulating glycoproteins.Methods in Mol.Medicine, Vol.9 "Lectin Methods and Protocols". Human Press Inc., 235-245 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sakurai,Y.et al.: "The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein lb-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom." Thromb.Haemost.79. 1199-1207 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hamako,J.et al.: "Purification and characterization of kaouthiagin,a von Willebrand factor-binding and cleaving metalloproteinase from Naja kaouthia cobra venom." Thromb.Haemost.80. 499-505 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Matsui and K.Titani.: "Methods in Mol.Medicine, Vol.9 “Lectin Methods and Protocols", eds by J.M.Rhodes and J.D.Milton" Humana Press Inc., 235-245 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松井太衛: "別冊 医学のあゆみ「血液疾病ーstate of arts」Ver.2 坂田、平井、溝口編" 医歯薬出版, 183-186 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsui,T.et al.: "Complete amino acid sequence of bitiscetin,a novel von Willebrad factor modulator protein purified from snake venom of Bitis arietans." Res.Commun.Biochem.Cell Mol.Biol.1(in press). (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsui,T.et al.: "Purification and amino acid sequence of halystase from snake venom of Agkistrodon halys biomhoffii,a serine protease specifically cleaving fibrinogen and kininogen." Eur.J Biochem.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsui,T.et al.: "Kaouthiagin,a metalloproteinase purified from Naja kaouthia cobra venom,specifically binds to and cleaves von Willebrand factor." Blood. 90. 466a-(abs) (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ozeki,Y.et al.: "D-Galactoside-specific lectins from the body wall of an echiuroid (Urechis unicinctus) and two annelids (Neanthes japonica and Marphysa sanguinea)." Comp.Biochem.Physiol.118B. 1-6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uchiyama,H.et al.: "Distribution and localization of galectin purified from Rana catesbeiana oocytes." Glycobiology. 7. 1159-1165 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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