1989 Fiscal Year Final Research Report Summary
Pathobiological Study on Congenital Deficiency of Vitamin K-dependent Protein S.
| Project/Area Number |
62480433
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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 |
Laboratory medicine
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| Research Institution | The University of Tokushima (1989)
Mie University (1987-1988) |
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Principal Investigator |
SUZUKI Koji Institute for Enzyme Research, University of Tokushima, 酵素科学研究センター, 教授 (70077808)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Protein S / Protein C / C4b-binding protein / Congenital protein S deficiency / Congenital thrombophilia / Protein C anticoagulant pathway / Vitamin K-dependent proteins / Monoclonal antibody |
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| Research Abstract |
[Aim] Protein S is a vitamin K-dependent plasma protein that plays a role as a cofactor for activated protein C (APC). APC is another vitamin K-dependent serine protease which inactivates blood coagulation cofactors, Factor Va and Factor VIIIa. Recently, patients with congenital deficiency of protein S or protein C have frequently been found as patients having severe thromboembolic diseases. Thus, protein S is involved in concert with APC in regulation of blood coagulation in vivo as well as in vitro. Recently, protein S in plasma was found to exist in two forms, one is a functionally active free form and the other is a functionally inactive complex form with a complement.component C4b-binding protein (C4bp) . The present study was performed to elucidate the pathobiology of protein S in patients with congenital deficiency of protein S.
[Results and Discussion] (1) Thirty seven patients in two families with congenital protein S deficiency were analyzed, then it was found that plasma protein S activity in these patients appeared to correlate with the amount of-free form protein S, but not with that of total protein S nor C4bp. (2) Seventeen monoclonal antibodies for C4bp were prepared and their epitopes on C4bp molecule were determined. Also a binding site for protein S on C4bp was determined. (3) Fifteen monoclonal antibodies for protein S were prepared and epitopes for the respective antibodies were determined. Enzyme immunoassay methods to determine free form protein S, total protein S and protein S-C4bp complex were established. (4) Function of protein S-C4bp complex was investigated and it was found that the complex inhibits competitively the interaction between free form protein S and APC which results in the decrease of cofactor activity of free form protein S. These results indicate that in plasma of patients with congenital deficiency of protein S, the cofactor activity of protein S depends on the amounts of both free form and complex form of protein S.
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[Publications] Iijima, K., Inoue, N., Nakamura, K., Fukuda, C., Ohgi, C., Okada, M., Mori, T., Nishioka, J., Hayashi, T. & Suzuki, K.: "Inherited deficiency of functional and free form protein S." Acta Haematol. Jpn. 52: 126-133, 1989.
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