| Project/Area Number |
06454646
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Fujita Health University |
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Principal Investigator |
TITANI Koiti Inst.for Comprehensive Med.Sci., Fujita Health University Professor, 総合医科学研究所, 教授 (60179942)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMURA Yoshihiro Department of Blood Transfusion, Nara Medical University, Professor, 輸血部, 教授 (80118033)
HAYASHI Nobuhiro Inst.for Comprehensive Med.Sci., Fujita Health University Research Associate, 総合医科学研究所, 助手 (80267955)
MATSUI Taei Inst.for Comprehensive Med.Sci., Fujita Health University Research Associate, 総合医科学研究所, 助手 (90183946)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Platelet adhesion / aggregation / von Willebrand factor / vWF modulator protein / GPIb-binding proteins / Extracellular matrix / Type III collagen / フォンビルブラント因子 / 血小板膜糖タンパク質(GP)Ib / ボトロセチン / ジャララカ GPIb-BP / アルボアグレギン-B / マムシギン / ビチスセチン / ジャララカGPIb-BP / トカラセチン / フラボセチンA,B / ビチスチン / ボトロンビン / フィブリノーゲン / コラーゲン / 高分子量出血性メタロプロテアーゼ / ジスインテグリン |
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| Research Abstract |
1) Purification, characerization and structure-function relationship of various snake venom proteins modulating platelet adhesion and aggregation : We have already purified and characterized "botrocetin", a von Willebrand factor (vWF) modulating protein, from the snake venom of Bothrops jararaca. In this study, we have isolated and characterized several other proteins with different functions from the same snake venom. These included 'bothrombin' which clots fibrinogen to fibrin, "jararhagin-C" with disintegrin-like activity which inhibits collagen-induced platelet aggregation and "jararaca GPIb-BP" with GPIb-binding activity which inhibits the interaction between vWF and platelets. GPIb-binding proteins have also been isolated from several other snake venoms. Their amino acid sequences have been determined and compared in detail to obtain some insight into the structure-function relationships. We have also isolated a protein with a strong botrocetin-like activity, termed "bitiscetin",
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from the Bitis arietans venom, and determined the amino acid sequence. The sequence homology, however, between botrocetin and bitiscetin is only 45%, suggesting the difference in their interaction mechanisms with vWF.2) Search for physiological vWF modulator : One of monoclonal antibodies raised against botrocetin, BCT-4-3, showed interaction with human endothelial cells and the reactivity was enhanced by addition of fibronectin. Botrocetin-like components immunopurified by immobilized BCT-4-3 from unbilical vein extracts were shown to consist essentially of fibronectin and a 130 kDa molecule. This complex is assumed to mimick botrocetin. 3) Interaction of vWF with extracellular matrix components : Only type III collagen among various extracellular matrix components specifically bound to vWF by an ELISA system. In static conditions, however, the interaction did not induced the interaction of vWF with glycocalicin, the extracellular domain of GPIb containing the vWF binding site, suggesting that another unknown physiological modulator may be involved in the platelet adhesion to extracellular matrix by vWF. Less
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