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1998 Fiscal Year Final Research Report Summary

Studies on protein S to develop the drugs for anti-coagulation and anti-inflammation

Research Project

Project/Area Number 08557064
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionMie University

Principal Investigator

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

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
Project Period (FY) 1996 – 1998
KeywordsProtein S / Protein S receptor / Protein S deficiency / C4b-binding protein / Activated protein C / Anticoagulants / Anti-inflammation / Sinusoid endothelial cells
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.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Gandrille,S.: "Protein S deficiency:A database of mutations"Thromb.Haemostas. 77. 1201-1214 (1997)

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

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishioka,J.: "Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles"J.Biol.Chem. 273. 11281 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi,T.: "Regulation of the human protein C inhibitor gene expression in HepG2 cells:Role of Spl and AP2"Biocyem.J. 332. 573-582 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wakita,T.: "Molecular cloning tissue distribution and androgen regulation of rat protein C inhibitor"FEBS Lett. 429. 263-268 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [Publications] Gabazza,E.C.: "Thrombin in the airways of athmatic patients"Lung. 177. 253-262 (1999)

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

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi,T.: "Organization and chromosomal localization of the human endothelial protein C receptor gene"Gene(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ido,M.: "Pulmonary Embolism"Springer-Verlag,Tokyo. 195 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Gandrille S, Borgel D, Suzuki K et al:: "Protein S deficiency: A database of Mutations"Thromb Haemostas. 77. 1201-1214 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gabazza EC, Takeya H, Suzuki K et al:: "Aquired activated protein C resistance in patients with lupus anticoagulant and essential thombocythemia"Clin Appl Thromb Hemostas. 3. 119-123 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishioka J, Ning M, 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. 273. 11281-11287 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi T, Usui M, Suzuki K:: "Regulation of the human protein C inhibitor gene expression in HepG2 cells: Role of Sp1 and AP2"Biochem J. 332. 573-582 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wakita T, Uhayashi T, Suzuki K: "Molecular cloning, tissue distribution and androgen regulation of rat protein C inhibitor"FEBS Lett. 429. 263-268 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi H, Gabazza EC, Suzuki K: "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
  • [Publications] Ido M, Hayashi T, Suzuki K: "Hereditary thrombophilia caused by abnormarity of the anticoagulant protein C pathway : Prenatal diagnosis of compound heterozygous protein C deficiency by direct detecion of mutaion sites"Pulmonary Embolism, Springer-Verlag, Tokyo. 21-35 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Gabazza EC, Taguchi O, Suzuki K: "Thrombin in the airways of asthmatic patients"Lung. 177. 253-262 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takagi M, Wada H, Suzuki K: "Increased activated protein C : protein C inhibitor complex and decrease protein C inhibitor levels in patients with chronic renal failure on maintenance hemodialysis"Clin Appl thromb Hemostas. 5. 113-116 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi T, Nakamura H, Suzuki K: "Organization and chromosomal localization of the human endothelial protein C receptor gene"GENE. in press. (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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