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Effects of chymase on limited proteolysis and activation of protein kinase on the mechanism of degranulation from mast cells

Research Project

Project/Area Number 62570113
Research Category

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

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionThe University of Tokushima, The Institute for Enzyme Research, Division of Enzyme Chemistry

Principal Investigator

HIROSHI Kido  The Univ. of Tokushima, The Inst. for Enzyme Res. Div. of Enzyme Chem., Assistant Professor, 酵素化学部門, 助手 (50144978)

Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsMast cell / Histamine / Degranulation / Chymase / Protein kinase C / Chymotrypsin inhibitor / トリプターゼ / ピネタミン / プロティンキナーゼ
Research Abstract

Two types of serine proteases, such as chymase and tryptase, are localized in the grnules of mast cells. We found that antibody of chymase, substrate analogues and specific inhibitor of chymase inhibited histamine release from rat mast cells but that inhibitors of tryptase did not. In addition specific inhibitors of chymase and anti-chymase F(ab')_2 also inhibited protein phosphorylation by protein kinase C after bridging of IgE-receptor. From these results, We speculate that chumase activates protein kinse C on the process of degranulation. After degranulation, chymase retained on the surface of mast cells. In order to clarify which of the chymase in the granules or on the cell surface is involved in histamine release, we examined the intra-cellular localization of the inhibitores of both histamine release and chymase, such as antichymase f(ab')_2 and ^<125>I-Bowman Burk soybean inhibitor. After incubation of these inhibitors with mast cells at 37゜C, they first bound to plasma membrane of mast cells and then were incorporated into the granules time-dependently, resulting in the inhibition of histamine release after bridging of IgE receptor. When these inhibitors were incubated with mast cells at 4゜C, they bound to plasma membrane but did not incorporated into the granules and did not also inhibit histamine release. These results show that incorporation of these inhibitors into the granules, in which chymase is localized, is essential for inhibition of histamine release by these inhibitors.Studies on the mechanisms of activation of protein kinase C by chymase and of protein phosphorylation by the activated protein kinase C are now in progress.

Report

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

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Naomi Fukusen: Biochem.Med.Metab.Biol.38. 165-169 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: Biol.Chem.Hoppe-Seyler. 369. 95-100 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yasuhisa Kato: J.Biochem.(Tokyo). 103. 820-822 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: J.Biol.Chem.263. 18104-18108 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nobuhiko Katunuma: J.Cell.Biochem.38. 291-301 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 木戸博: 最新医学社. 43. 770-775 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 木戸博: 代謝. 25. 187-192 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 木戸博: 細胞工学. 17. 851-857 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Mechanism and Regulation of Intracellular Proteolysis" Japan Sci.Soc.Press, 11 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Naomi Fukusen: "Kinetic studies on the inhibitions of mast cell chymase by natural serine protease inhibitors: Indications for potential biological functions of these inhibitors" Biochem. Med. Metab. Biol.38. 165-169 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Antibodies and inhibitor of chymase are incorporated into mast cell granules and inhibit histamine release" Biol. Chem. Hoppe-Seyler. 369. 95-100 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Yasuhisa Kato: "Peptide boronic acids, substrate analogs, inhibit chymase, and histamine release from rat mast cells" J. Biochem. (Tokyo). 103. 820-822 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Kunitz-type protease inhibitor found in rat mast cells (purification, properties, and amino acid sequence)" J. Biol. Chem.263. 18104-18108 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nobuhiko Katunuma: "Biological functions of serine proteases in mast cells in allergic inflammation" J. Cell. Biochem.38. 291-301 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: "The role of proteases and protease inhibitors in allergic inflammation" Saishinigaku. 43. 770-775 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Serine proteases in mast cells and allergic inflammation" Taisha. 25. 187-192 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Intracellular kunitz-type inhibitors as biomodulators: Focused on trypstatin" Cell Technology. 17. 851-857 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Kido: Biological Functions of Chymase and Tryptase and Their Inhibitors in Rat Mast Cells. Japan Sci. Soc. Press, 11 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Naomi Fukusen: Biochem.Med.Metab.Biol.38. 165-169 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hiroshi Kido: Biol.Chem.Hoppe-Seyler. 369. 95-100 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yasuhisa Kato: J.Biochem.(Tokyo). 103. 820-822 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hiroshi Kido: J.Biol.Chem.263. 18104-18108 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Nobuhiko Katunuma: J.Cell.Biochem.38. 291-301 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 木戸博: 最新医学社. 43. 770-775 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 木戸博: 代謝. 25. 187-192 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 木戸博: 細胞工学. 17. 851-857 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hiroshi Kidoi: "Mechanism and Regulation of Intracellular Proteolysis" Japan Sci.Soc.Press, (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Naomi Fukusen: Biochem. Med. Metab. Biol.38. 165-169 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hiroshi Kido: Biol. chem. Hoppe-Seyler. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yasuhisa Kato: J. Biochem.(1988)

    • Related Report
      1987 Annual Research Report

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

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