| Project/Area Number |
03454540
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
物質生物化学
|
|---|
| Research Institution | Fujita Health University |
|---|
Principal Investigator |
TITANI Koiti Fujita Health University, Inst.for Comprehensive Med.Sci., Professor, 総合医科学研究所, 教授 (60179942)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJIMURA Yoshihiro Department of Blood Transfusion, Nara Medical College, Associate Professor, 輸血部, 助教授 (80118033)
MATSUI Taei Inst.for Comprehensive Med.Sci., Instructor, 助手 (90183946)
関口 清俊 大阪府立母子保健総合医療センター研究所, 病因病態部門, 部長 (50187845)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1991: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
|---|
| Keywords | Platelet Aggregation / von Wellebrand Factor / Botrocetin / Ristocetin / Lectin / Bothrombin / alpha-Thrombin / Fibrinogen / 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 |
|---|
| Research Abstract |
Isolation and Chemical Cahracterization of Two-chain Botrocetin : Two-chain Botrocetin, the von Willebrand factor (vWF) - dependent platelet coagglutinin, was purified from the venom of the snake Bothrops jararaca and characterized structurally and functionally (Biochemistry(1991)30,1957-1964). Two-chain botrocetin is a heterodimer composed of the alpha-subunit(133 amino acid residues)and the beta-subunit(125 amino acid residues)held together by a disulfide bond. In terms of amino acid sequence and disulfide bond location, it is homologous to C-type(Ca^<++> -dependent)lectins(Proc.Natl.Acad.Sci.(1993) 90,928-932). However, the activity of botrocetin in promoting vWF binding to platelets is not inhibited by EDTA or lactose and other sugars.
Out of several anti-human vWF monoclonal antibodies which inhibit ristocetin-induced platelet aggregation, only two antibodies inhibited botrocetin-induced aggregation, indicating that the binding sites on vWF of ristocetin and botrocetin are closely located but distinct (Thromb.Haemostasis(1992)68,464-469).
Structure and Function of Bothrombin : A fibrinogen clotting enzyme, termed "Bothrombin, was isolated from the venom of Bothrops jararaca and cahracterized structurally and functionally. Bothrombin is composed of a single polypeptide of 232 amino acid residues with 3 Asn-linked sugar chains. DEP totally abolished its activity, but hirudin had negligible effect on bothrmbin activity. Unlike alpha-thrombin, bothrombin split off fibrinopeptide A without releasing fibrinopeptide B.Bothrombin activated blood coagulation factor VIII, but its activity was much lower than alph-thrombin. Bothrombin did not induce platelet aggregation by itself, but did aggregate platelets in the presence of exogenous fibrinogen (Biochemistry(1994)33, 1843-1849).
|
