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Structure-function relationship of the endothelial cell membrane receptors playing in the anti-thrombotic properties.

Research Project

Project/Area Number 12480179
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 Professor, 医学部, 助手 (00242959)
TAKEYA Hiroyuki  Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (60222105)
IDO Masaru  Mie University Hospital, Associate Professor, 医学部・附属病院, 助教授 (90167263)
KAMADA Haruhiko  Mie University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00324509)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2000: ¥10,200,000 (Direct Cost: ¥10,200,000)
Keywordsendothelium / anti-thrombotic property / protein structure-function relationship / aspirin / adenosine receptor / thrombomodulin / protein C receptor / tissue factor / 血管内皮細胞 / 細胞膜受容体 / アデノシン / NO産生酵素 / cGMP / cAMP
Research Abstract

The anti-thrombotic properties of the endothelium are 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 receptors on the endothelial cell membrane playing in the anti-thrombotic functions. Here we studied the following subjects :
(1)Effect of adenosine (Ado) on the tissue factor (TF) expression induced by lipopolysaccharide and or thrombin. Ado was found to inhibit TF expression via stimulating the endothelial nitric oxide synthase (eNOS) mRNA expression and also enzymatic activity. (2) Effect of aspirin and sodium salicylates (Sal) on the anti-thrombotic activity of Ado. Sal was shown to enhance the Ado production and increased extracellular level of Ado stimulates Ado receptor resulting in the decrease of TF expression in the thrombin-stimulated endothelial cells Sal and Ado may inhibit the NF_<-κ>B activation in the cells. (3) Gene structure analysis of the endothelial protein C receptor (EPCR) and thrombomodulin (TM) of the patients who have thrombotic episodes to understand the structure-function relationship of EPCR and TM. A series of these studies may highlight the molecular bases of the anti-thrombotic properties of the endothelial cells.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Hori, H.: "Insulin resistance is associated with increased circulating level of thrombin-activatable fibrinolysis inhibitor in type 2 diabetic patients"J. Clin. Endoc. Metabol.. 87. 660-665 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gabazza, E.C.: "Adenosine inhibits thrombin-induced expression of tissue factor on endothelial cells by a nitric oxide-mediated mechanism"Clin. Science. 102. 167-175 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi, T.: "Long-term inhalation of high-dose of nitric oxide increases intraalveolar activation of coagulation system in mice"Am. J. Respir. Crit. Care Med.. 163. 1676-1682 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui, H.: "Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse"Am. J. Respir. Crit. Care Med.. 163. 1660-1668 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuneyoshi, N.: "Expression and anricoagulant function of the endothelial cell protein C receptor (EPCR) in cancer cell lines"Thromb. Haemost.. 85. 356-361 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki, K.: "Protein C inhibitor (PAI-3):structure and multi-function"Fibrinol. Proteol.. 14. 133-145 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 鈴木 宏治: "Vascular Biolobyナビゲーター"メディカルレビュー社. 373 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hori, Y., et al: "Insulin resistance is associated with increased circulating level of thrombin-activatable fibrinolysis inhibitor in type 2 diabetic patients"J. Clin. Endoc. Metabol.. 87. 660-665 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gabazza, E. C., et al: "Adenosine inhibits thrombin-induced expression of tissue factor on endothelial cells by a nitric oxide-mediated mechanism"Clin. Science. 102. 167-175 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi, T., et al: "Long-term inhalation of high-dose of nitric oxide increases intraalveolar activation of coagulation system in mice"Am. J. Respir. Crit. Care Med.. 163. 1676-1682 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui, H., et al: "Intratracheal administration of activated protein C inhibits bleopmycin-induced lung fibrosis in the mouse"Am. J. Respir. Crit Care Med.. 163. 1660-1668 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuneyoshi, N., et al: "Expression and anricoagulant function of the endothelial cell protein C receptor (EPCR) in cancer cell lines"Thromb. Haemost. 85. 356-361 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki, K.: "Protein C inhibitor (PAI-3) : structure and multi-function"Fibrinol. Proteol.. 14. 133-145 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimizu, S., et al: "Thrombin stimulates the expression of PDGF in lung epithelial cells"Am. J. Respit. Cell Mol. Biol.. 279. L503-L510 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Watanabe, R., et al: "Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable state"Am. J. Hematol.. 65. 35-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, R., et al: "Coagulation and fibrinolytic activities in 2 siblings with β2-glycoprotein I deficiency"Blood. 96. 1594-1595 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oka, S., et al: "Role of activated protein C in Helicobacter Pylori-associated gastritis"Infect. Immun.. 68. 2863-2869 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki, K. and Hayashi, T.: "Cis-elements required for expression of human protein C inhibitor (PCI) gene in HepG2 cells and its androgen-dependent expression in rat reproductive organs"Sem. Thromb. Hemost. 26. 75-84 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuasa, H., et al.: "Bovine protein C inhibitor has a unique reactive site and can transiently inhibit plasmin"Thromb. Haemost. 83. 262-267 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kise, H., et al.: "Measurement of protein C inhibitor in seminal plasma is useful for detecting agenesis of seminal vesicles or the vas defens"J. Andrology. 21. 201-212 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ido, M., et al: "Identification of a novel 33-kDa Ser/Thr kinase that phosphorylates the cytoplasmic tail of protease-activated receptor-1 (thrombin receptor) in human platelets"Thromb. Haemost. 83. 617-621 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhou, H., et al.: "Prothrombin promotes the invasiveness of melanoma cells by a different mechanism from thrombin"Fibrinol. Proteol.. 13. 272-278 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hori, H.: "Insulin resistance is associated with increased circulating level of thrombin-activatable fibrinolysis inhibitor in type 2 diabetic patients"J.Clin.Endoc.Metabol.. 87. 660-665 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gabazza, E.C.: "Adenosine inhibits thrombin-induced expression of tissue factor on endothelial cells by a nitric oxide-mediated mechanism"Clin.Science. 102. 167-175 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi, T.: "Long-term inhalation of high-dose of nitric oxide increases intraalveolar activation of coagulation system in mice"Am.J.Respir.Crit.Care Med.. 163. 1676-1682 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui, H.: "Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse"Am.J.Respir.Crit.Care Med.. 163. 1660-1668 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuneyoshi, N.: "Expression and anricoagulant function of the endothelial cell protein C receptor(EPCR)in cancer cell lines"Thromb.Haemost.. 85. 356-361 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki, K.: "Protein C inhibitor(PAI-3):structure and multi-function"Fibrinol.Proteol.. 14. 133-145 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 鈴木 宏治: "Vascular Biolobyナビゲーター"メディカルレビュー社. 373 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuncyoshi,N.: "Expression and anticoagulant function of the endothelial cell protein C receptor (EPCP) in cancer cell lines."Thromb.Haemost.. 85. 356-361 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi,R.: "Coagulation and fibrinolytic activities in 2 siblings with β2-glycoprotein I deficiency."Blood. 96. 1594-1595 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oka,S.: "Role of activated protein C in helicobacter pylori-associated gastritis."Infect.Immunity.. 68. 2863-2869 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ido,M.: "Identification of a novel 33-kDa Ser/Thr kinase that phosphorylates the cytoplasmic tail of protease-activated redceptor 1 (thrombin receptor) in human platelets."Thromb.Haemost.. 83. 617-621 (2000)

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

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,R.: "Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states."Am.J.Hematol.. 65. 35-40 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木宏治: "最新・分子動脈硬化学"メディカルレビュー社. 511 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木宏治: "血液検査 実践マニュアル"医学書院. 994 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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