The mechanism of the initiation ractions for the intrinsic blood coagulation,kinin release and fibrinolysis: the activation mechanism of the precursor of serine proteases by negatively-charged surfaces and gheir biological significance.
| Project/Area Number |
61480462
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
KATO Hisao National Cardiovascular Center Research Ilnstitute, 室長 (80029959)
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| Co-Investigator(Kenkyū-buntansha) |
OH-ISHI Sachiko School of Pharmaceutical Sciences, Kitasato University, 薬学部, 教授 (70050416)
MATSUDA Takehisa National Cardiovascular Center Research Institute, 部長 (60142189)
ENJYOJI Kei-ichi National Cardiovascular Center Research Institute, 研究員 (00194027)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1986: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Blood coagulation / initiation reaction / kinin release / 線溶系 / 接触反応 |
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| Research Abstract |
The initiation reaction of the intrinsic blood coagulation is triggered by the interaction of a precursor of serine protease, Factor XII, with negativelycharged surfaces, which leads to the transformation of the precursor to active protease. This reaction is also the initiation reactions of the fibrinolytic system and kinin-releasing system. Although these reactions are considered to play important roles in the hemostasis, their biological significance remains to be established. This study was undertaken to clarify, (1) how the limited proteolysis of the precursors of serine proteases is caused after the interaction with negatively-charged surfaces and (2) what the biological significance of the activation reaction of Factor XII is.
The results are as follows;
(1) The initiation reactions of the intrinsic blood coagulation were reconstituted by the combination of ghe purified coagulation factors and the sensitive method to measure the activation of Factor XII was established. The activation reactions with kaolin, sulfatide and polysaccharide sulfate were found to be dependent not only on the concentrations of the surfaces and the coagulation factors, but also on the concentration of metal ions, particularly, zinc ion, and of sodium chloride. Platelets showed the strong inhibitory activity to the reactions by the interaction of the surfaces with the cationic proteins liberated from platelets.
(2) We established the radioimmunoassay method for kininogens and andalyzed the kininogens (T-kininogens) which increased by the induction of inflammation using normal and HMW kininogen-deficient rats. We also analyzed the intrinsic blood coagulation and the activation of prekallikrein in the plasmas of rat, guineapig, ox, rabbit and sunkus, comparing with those of human plasma. We could find that some animals such as guinea-pig and rat are very sensitive in the activation of Factor XII and that some animals such as ox, rabbit and sunkus are very resistant in the actilvation.
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Report
(2 results)
Research Products
(22 results)
