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Molecular biological studies on the blood fluidity - Structure-function relationship of the endothelial receptors playing in the anticoagulant protein C pathway

Research Project

Project/Area Number 09480149
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionMie University

Principal Investigator

SUZUKI Koji  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70077808)

Co-Investigator(Kenkyū-buntansha) HAYASHI Tatsuya  Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (00242959)
IDO Masaru  Mie University, Hospital, Associate Professor, 医学部・附属病院, 助教授 (90167263)
武谷 浩之  三重大学, 医学部, 助手 (60222105)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥7,500,000 (Direct Cost: ¥7,500,000)
Keywordsprotein C pathway / protein C / protein S / protein C inibitor / blood fluidity mechanism / endothelial cells / protein C receptor / protein S receptor / 抗血栓性因子 / 血液凝固因子 / トロンボモジュリン / 細胞膜受容体 / 抗血栓性機構 / 血液流動性機構 / 遺伝子発現調節 / 血栓症 / トロンボモジュリン異常症 / プロテインC受容体異常症
Research Abstract

The anticoagulant protein C pathway is one of the most important systems to maintain the vascular blood fluidity. The aim of this project is to clarify the structure-function relationship of the several endothelial receptors playing in the anticoagulant protein C pathway to understand the molecular mechanism of the blood fluidity. Here we studied the following eight subjects : (1) Molecular cloning of the human endothelial protein C receptor (EPCR) gene. (2) Molecular mechanism of expression of human protein C inhibitor (PCI) gene, particularly in hepatocyte cells. (3) Mechanism of expression of the regulatory activity of PCI secreted from α granules of human platelets. (4) Structure-function relationship of the PCI and difference of its tissue specific mRNA expression among various species ; humans, monkeys, rabbits, bovines, rats and mice. (5) The role of the factors involved in the anticoagulant protein C pathway in the pathogenesis associated with various diseases. (6) The molecular mechanism to maintain the anticoagulant ability of the endothelium by adenosine and NO. (7) Effect of thrombin on the and prothrombin on the metastasis of tumor cells. (8) Identification and isolation of protein S receptor from human endothelial cells. These studies may highlight the mechanism of blood fluidity by the anticoagulant protein C pathway.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (64 results)

All Other

All Publications (64 results)

  • [Publications] Kise, H.: "Measurement of protein C inhibitor in seminal plasma is useful for detecting agenesis of seminal vesicles or the vas defens"J. Andrology. 21. 207-212 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sana, T.: "The zymogen prothrombin stimulates cell locomotion and calcium influx in murine osteosarcoma cells by different mechanism from thrombin"Int. J. Oncology. 15. 1197-1203 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi, T.: "Organization and chromasomal localization of the human endothelial protein C gene"Gene. 238. 367-373 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Saito, Y.: "Change of plasma hemostatic markers during percutaneous transluminal coronary angioplasty in patients with chronic coronary artery disease"Am. J. Hematol.. 61. 238-242 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gabazza, E. C.: "Thrombin in the airways athmatic patients"Lung. 117. 253-262 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi, M.: "Increased activated protein C : protein C inhibitor complex levels in patients with chroni renal failure on maintenance hemodialysis"Clin. Appl. Thromb. Hemost.. 5. 113-116 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida, K.: "Phylloquinone and menaquinone concentrations in plasma, liver and feces of beagle dogs after birth"Bioscience Microflora. 18. 37-42 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wakita, T.: "Molecular cloning, tissue distribution and androgen regulation of rat protein C inhibitor"FEBS Lett.. 429. 263-268 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhou, H.: "Prothrombin and its derivatives stimulate motility of melanoma cells"Thromb. Haemost.. 80. 407-412 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi, T.: "Regulation of the human protein C inhibitor gene expression in HepG2 cells : Role of Sp1 and AP2"Biochem. J.. 332. 573-578 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Deguchi, H.: "Adnoshine regulates tissue factor expression on the endothelial cells"Thromb. Res.. 91. 57-64 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, H.: "Protein C anticoagulant system in patients with interstitial lung disease"Am. J. Respit. Crit Care Med.. 157. 1850-1854 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Usui, M.: "Molecular cloning, expression and tissue distribution of canine lipopolysaccharide (LPS)-binding protein"Biochim. Biophys. Acta. 1397. 202-212 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishioka, J.: "Protein C inhibitor secreted from activatied platelets dfficiently inhibits activated protein C on phosphatidyl-ethanolamine of platelet membrane and microvesicles"J. Biol. Chem.. 273. 11281-11287 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gandrille, S.: "Protein S deficiency : A database of mutations- for the plasma coagulation inhibitors subcommittee of the Scientific and Standardization of the International Society on Thrombosis and Haemostasis"Thromb. Haemost.. 77. 1201-1214 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Deguchi, H.: "Dilazep, an adenosine poteniator, inhibits tissue factor expression in the endothelial cells stimulated with tumor factor-α, thrombin or phorbol 12-myristate 13-acetate"Blood. 90. 2345-2356 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takeya, H.: "Anti-β2-glycoprotein I(β2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the β2GPI binding to phospholipids"J. Clin. Invest.. 99. 2260-2268 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gabazza, E. C.: "Aquired activated protein C resistance in patients with lupus anticoagulant and essential thrombocythemia"Clin. Appl. Thromb. Hemost.. 3. 119-123 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Deguchi, H.: "Kringle 1 domain of prothrombin interacts with factor Va during the assembly of the prothrombinase complex"Biochim. J.. 321. 729-735 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gabazza, E. C.: "Protein C activation in NIDDM patients"Diabetologia. 39. 1455-1461 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kise, H., et al.: "Measurement of protein C inhibitor in seminal plasma in useful for detecting agenesis of seminal vesicles or the vas defense"J. Andrology. 21. 207-212 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sano, et al.: "The zymogen prothrombin stimulates cell locomotion and calcium influx in murine osteosarcoma cells by different mechanism from thrombin"Int. J. Oncology. 15. 1197-1203 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi, T., et al.: "Organization and chromasomal localization of the human endothelial protein C gene"Gene. 238. 367-373 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Saito, Y., et al.: "Change of plasma hemostatic markers during percutaneous transluminal coronary angioplasty in patients with chronic coronary artery disease"Am. J. Hematol.. 61. 238-242 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gabazza, E.C., et al.: "Thrombin in the airways athmatic patients"Lung. 177. 253-262 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi, M., et al.: "Increased activated protein C : protein C inhibitor complex levels in patients with chroni renal failure on maintenance hemodialysis"Clin Appl. Thromb. Hemost.. 5. 113-116 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida, K., et al.: "Phylloquinone and menaquinone concentrations in plasma, liver and feces of beagle dogs after birth"Bioscience Microflora. 18. 37-42 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wakita, T., et al.: "Molecular cloning, tissue distribution and androgen regulation of rat protein C inhibitor"FEBS Lett.. 429. 263-268 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki, K.: "Hereditary thrombophilia caused by abnormarity of the anticoagulant protein C pathway : Prenatal diagnosis of compound heterozygous protein C deficiency by direct detection of mutation sites"Pulmonary Embolism (eds. Nakano, T. & Goldhaber, S. Z.) Springer-Verlag, Tokyo. 21-35 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhou, H., et al.: "Prothrombin and its derivatives stimulate motility of melanoma cells"Thromb Haemost. 80. 407-412 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi, T., et al.: "Regulation of the human protein C inhibitor gene expression in HepG2 cells : Role of Sp1 and AP2"Biochem. J.. 332. 573-578 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Deguchi, H., et al.: "Adenoshine regulates tissue factor expression on the endothelial cells"Thromb. Res.. 91. 57-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi, H., et al.: "Protein C anticoagulant system in patients with interstitial lung disease"Am. J. Respit. Crit Care Med. 157. 1850-1854 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Usui, M., et al.: "Molecular cloning, expression and tissue distribution of canine lipopolysaccharide (LPS)-binding protein"Biochim. Biophys. Acta. 1397. 202-212 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishioka, J., et al.: "Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidyl-ethanolamine of platelet membrane and microvesicles"J. Biol. Chem.. 273. 11281-11287 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gandrille, S., et al.: "Protein S deficiency : A database of mutations - for the plasma coagulation inhibitors subcommittee of the Scientific and Standardization of the International Society on Thrombosis and Haemostasis"Thromb. Haemost.. 77. 1201-1214 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Deguchi, H., et al.: "Dilazep, an adenosine potentiator, inhibits tissue factor expression in the endothelial cells stimulated with tumor necrosis factor-α, thrombin or phorbol 12-myristate 13-acetate"Blood. 90. 2345-2356 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takeya, H., et al.: "Anti-β2-glycoprotein I (β2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the β2GPI binding to phospholipids"J. Clin. Invest.. 99. 2260-2268 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gabazza, E.C., et al.: "Acquired activated protein C resistance in patients with lupus anticoagulant and essential thrombocythemia"Clin. Appl. Thromb. Hemost.. 3. 119-123 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Deguchi, H., et al.: "Kringle 1 domain of prothrombin interacts with factor Va during the assembly of the prothrombinase complex"Biochem. J.. 321. 729-735 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Gabazza, E.C., et al.: "Protein C activation in NIDDM patients"Diabetologia. 39. 1455-1461 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhou,H.: "Prothrombin promotes the invasiveness of melanoma cells by a different mechanism from thrombin"Fibrinol.Proteol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ido,M.: "Thrombin receptor-associated 33-kDa serine/threonine kinase phosporylates the cytoplasmic tail of thrombin receptor in human platelets"Thromb.Haemost.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki,K.: "Cis-elememts required for expression of human protein C inhibitor (PCI) gene in Hepg2 cells and its androgen-dependent expression in rat reproductive organs"Sem.Thromb.Haemost.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuasa,H.: "Bovine protein C inhibitor has a unique reactive site and can transiently inhibit plasmin"Thromb.Haemost.. 83. 262-267 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sano,T.: "Thrombin receptor-associated 33-kDa serine/threonine kinase phosporylates the cytoplasmic tail of thrombin receptor in human platelets"Int.J.Oncol.. 15. 1197-1203 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki,K.: "Pulmonary Embolism"Springer. 195 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木宏治: "広範囲 血液・尿化学検査,免疫学的検査(2)"日本臨牀社. 829 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zhou,H.: "Prothrombin and its derivatives stimulate motility of melanoma cells." Thromb.Haemostas.80. 407-412 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wakita,T.: "Molecular cloning,tissue distribution and androgen regulation of rat protein C inhibitor." FEBS.Lett.429. 263-268 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi,T.: "Regulation of the human protein C inhibitor gene expression in HepG2 cells: Role of Sp1 and AP2." Biochem.J.332. 573-582 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Deguchi,H.: "Adenosine regulates tissue factor expression on the endothelial cells." Thromb.Res.91. 57-64 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishioka,J.: "Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidy-lethanol amine of platelet membrane and microvesicles." J.Biol.Chem.273. 11281-11287 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi,H.: "Decreased intra-alveolar activation of the protein C anticoagulant system in patients with interstitial lung disease." Am.J.Resp.Crit.Care Med.157. 1850-1854 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鈴木 宏治: "血液" 先端医学社, 241 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鈴木 宏治: "実践臨床検査医学" 文光堂, 489 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi,T., Usui,T., Suzuki,K., et al.: "Regulation of the human protein C inhibitor gene expression in HepG2 cells:Role of Spl and AP2." Biochem.J.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishioka,J., Ma,N., Suzuki,k., et al.: "Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles." J.Biol.Chem.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Usui,M., Hayashi,T., Suzuki,K., et al.: "Canine lipopolysaccharide-binding protein:cDNA cloning and its tissue distribution of canine model of extended hepatectomy." Biochim.Biophys.Acta. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Deguchi,H., Takeya,H., Suzuki,K., et al.: "Dilazep,an adenosine potentiator, inhibits tissue factor expression in the endothelial cells stimulated with tumor necrosis factor-α,thrombin or phorbol 12-myristate 13-acetate." Blood. 90. 2345-2356 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeya,H., Mori,T., Suzuki,K., et al.: "Anti-β2-glycoprotein I(β2GPI)monoclonal antibodies with lupus anticoagulant-like activity enhance the β2GPI bindong to phospholipids." J.Clin.Invest.99. 2260-2268 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Deguchi,H., Takeya,H., Suzuki,K., et al.: "Kringle I domain of prothrombin interacts with factor Va during the assembly of the prothrombinase complex." Biochem.J.321. 729-735 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鈴木 宏治: "Annual Review 血液 1998" 中外医学社(高久 史麿 他編), 245(10) (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鈴木 宏治: "DIC Ology" メジカルレビュー社(丸山 征郎 編), 490(17) (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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