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Analysis of the mechanism of endothelial cell -dependent activation of plasminogen activator inhibitor

Research Project

Project/Area Number 62570553
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical School

Principal Investigator

SAKATA Yoichi  Jichi Medical School, 医学部, 助教授 (40129028)

Co-Investigator(Kenkyū-buntansha) TERUKINA Shigeharu  Jichi Medical School, 医学部, 講師 (80146159)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsendothelial cells / plasminogen activator / plasminogen activator inhibitor / プラスミノゲンアクチベータインヒビタ / vitronectin / プラスミノゲンアクチベータ / α_2プラスミンインヒビタ
Research Abstract

Endothelial cells (ECS) are modulators of hemostasis, thrombosis and fibrinolysis. Not only they produce coagulation factors but they produce tissue type plasminogen activator (t-PA) which is physiologically important activator of plasminogen on the surface of fibrin and ECs. In addition, recently, it has become clear that t-PA activity is controlled by a specific, fast- acting plasminogen activator inhibitor 1 (PAI-1) which is produced by ECs. Interestingly, two different forms of this PAI-1 have been found in medium conditioned by cultured ECs: a fast-acting active form (only a few %) and 20-fold excess of latent form that is inactive but can be activated by denaturants. In a test fube, even when we added a large amount of t-PA to conditioned medium, we could observe only a small amount of t-PA/PAI-1 complex generated in a test tube. However, we found that the addition of increasing concentrations of t-PA to confluent ECs produced a satorable, dose-dependent increase of the activator/PAI-1 complex. We analyzed these results in cultured ECs system by using actinomycin D to prevent synthesis, [^<35>S] Methionine labeling of ECs proteins, porous bottom culture dish (Transwell) to prevent t-PA directly interact with proteins on the surface of ECs.
Taking our results and previous observations, we can conclude that latent PAI-1 could not be activated in the presence of t-PA and ECs but PAI-1, as an active form, bound to some binding protein on the surface of ECs or the extracellular matrix and the reaction between PA and PAI-1 mainly occurs on the ECs.
Furthermore, one possible candidate of binding proteins may be vitronectin/total PAI-1 in conditioned medium. However, we were unable to demonstrate ECs-associated vitronectin directly bt immunohistochemical method and vitronectin is a very sticky protein. So, we are now trying to determine the identity of receptor protein and vitronectin and to clarify the binding site between PAI-1 and vitronectin.

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 坂田洋一: 日血会誌. 50. 1379-1382 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: Fibrinolysis. 2. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: J.Biol.Chem.263. 1960-1969 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: Blood.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: Blood.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: Blood.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: "Effect of activated protein C on the fibrinolytic components released by cultured bovine aortic endothelial cells." Fibrinolysis. 2. 7-15 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: "Interaction of tissue-type plasminogen activator and plasminogen activator inhibitor 1 on the surface of endothlial cells." J. Biol. Chem.263. 1960-1969 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: "Clot-lysis induced by monoclonal antibody against _2 -plasmin inhibitor." Blood.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: "Role of plasminogen activator inhibitor in clot lysis." Blood.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: "Characterization of plasminogen activator inhibitor in human megakaryocytic cell line; CMK." Blood.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yoichi Sakata: Fibrinolysis. 2. 7-15 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoichi Sakata: J.Biol.Chem.263. 1960-1969 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoichi Sakata: Blood.

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoichi Sakata: Blood.

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoichi Sakata: Blool.

    • Related Report
      1988 Annual Research Report
  • [Publications] Yuichi Kamikubo: Biochim.Biophys.Acta.

    • Related Report
      1988 Annual Research Report
  • [Publications] Yoichi Sakata: Fibrinolysis.

    • Related Report
      1987 Annual Research Report
  • [Publications] Yoichi Sakata: Journal of Biological Chemistry. 263. 1960-1969 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yutaka Eguchi: Journal of Biological Chemistry.

    • Related Report
      1987 Annual Research Report
  • [Publications] Yoichi Sakata: Journal of Clinical Investigation.

    • Related Report
      1987 Annual Research Report
  • [Publications] Masayuki Okada: Biochemistry.

    • Related Report
      1987 Annual Research Report
  • [Publications] Masayuki Okada: Biochimica et Biophysica Acta.

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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