1998 Fiscal Year Final Research Report Summary
Studies on the physiological function of sugar chains and the activation mechanism of human von Willebrand factor
| Project/Area Number |
09671139
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Fujita Health University |
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Principal Investigator |
MATSUI Taei Fujita Health U.Inst.Comprehensive Med.Sci., Associate Prof., 総合医科学研究所, 講師 (90183946)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | von Willebrand factor / blood group antigen / bone marrow transplantation / platelet / snake venom / protease / amino acid sequence / lectin |
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| 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.
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