1998 Fiscal Year Final Research Report Summary
Studies on protein S to develop the drugs for anti-coagulation and anti-inflammation
| Project/Area Number |
08557064
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Hematology
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| Research Institution | Mie University |
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Principal Investigator |
SUZUKI Koji Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70077808)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Masataka Nihon Pharmaceutical Co.,R & D Division, Reserch head, 研究開発本部・東京研究部, 主幹研究員
HAYASHI Tatsuya Mie University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00242959)
IDO Masaru Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (90167263)
HONJO Eijiro Nihon Pharmaceutical Co.,R & D Division, Resercher, 研究開発本部・東京研究部, 研究員
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| Project Period (FY) |
1996 – 1998
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| Keywords | Protein S / Protein S receptor / Protein S deficiency / C4b-binding protein / Activated protein C / Anticoagulants / Anti-inflammation / Sinusoid endothelial cells |
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| Research Abstract |
Protein S, a vitamin K-dependent plasma glycoprotein, plays as anticoagulants by enhancing the activated protein C-catalyzed inactivation of coagulation factors Va and VIIIa, and also by inhibiting the prothrombinase complex formation. Protein S also plays as an anti-inflammatory agent in the in vivo study using experimental animal models. In this project, we studied structural and functional features of protein S to develop protein S as a drug in-aid for anticoagulation and anti-inflammation: (1) We found that rat protein S mRNA expresses strongly in the liver and weakly in the lung, spleen testis and uterus, and that rat plasma protein S and C4b-binding protein (C4BP) behave similarly to human counterparts. The levels of protein S and C4BP in the isolated liver cells were specifically increased by treating with IL-6, and decreased by treating with lipopolysaccharide. These change of protein S was also observed in the isolated sinusoid endothelial cells. Thus the expression of protein S from the sinusoid cells may reflect the level of plasma protein S. (2) We found that protein S receptor exits specifically on the human endothelial cells, and that the receptor is different from annexin II that have been recently reported as a candidate for protein S receptor on vascilar smooth muscle cells.
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