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Studies on the analysis of molecular structure and signal-transduction mechanism of the cell-membrane damaging by staphylococcal cytolytic toxins.

Research Project

Project/Area Number 63480150
Research Category

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

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionChiba University

Principal Investigator

KATO Iwao  Chiba University, School of Medicine, Professor, 医学部, 教授 (40012702)

Co-Investigator(Kenkyū-buntansha) KAMIO Yoshiyuki  Tohoku University, Faculty of Agriculture Assistant Professor, 農学部, 助教授 (00109175)
MORINAGA Naoko  Chiba University, School of Medicine Assistant, 医学部, 助手 (20092108)
NODA Masatoshi  Chiba University, School of Medicine Assistant Professor, 医学部, 助教授 (60164703)
畝本 力  千葉大学, 薬学部, 教授 (30089601)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1989: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1988: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsStaphylococcal alpha-toxin / Leukocidin S and F comp. / ADP-ribosyltransferase / Phospholipase A_2 / Phospholipase C / GTP-binding protein / HL-60 cells / ヒト前骨髄性白血病HL-60細胞 / ブドウ球菌α毒素 / ロイコシジンS成分 / ロイコシジンF成分 / ホスホリバーゼA_2 / ホスホリパーゼC / ホスファチジルコリン / ホスファチジルイノシトール / NAD
Research Abstract

1. After binding of the highly purified staphylococcal alpha-toxin to rabbit erythrocyte or polymorphonuclear leukocyte (neutrophile) membranes, the alpha-toxin rapidly stimulated the activities of phospholipase A_2 and inositol phospholipid specific phospholipase C, respectively, in the presence of NAD and GTP. Thereafter, it was shown that 37 K and 41 K GTP-binding proteins ADP-ribosylated by the ADP-ribosyltransferase of the alpha-toxin transmitted the activating signal to these phospholipases A_2 and C.
2. Staphylococcal leukocidin consists of two components (S and F) which are inactive when tested alone, but act synergistically to cause lysis of ngutophiles and macrophages of rabbits and humans. An ADP,-ribosylation of 37 K GTP-binding protein by the S component which possesses an ADP-ribosyltransferase activity resulted in the stimulation of phospholipase A_2 activity in the presence of NAD and GTP.
3. Staphylococcal leukocidin F component having an ADP-ribosyltransferase stimulated the activity of inositol phospholipid specific phospholipase C in the presence of NAD and GTP resulting from the ADP-ribosylation of a molecular weight of 41 K GTP-binding protein by the F component.
The susceptibility of human promyelocytic leukamia HL-60 cells to the cytotoxic activity of leukocidin changed depending on the degree of differentiation induced by TPA. The cytotoxic activity of HL-60 cells treated with TPA for 6 hours was more required for a 50-fold dose of leukocidin than that of the mature macrophage-like cells have been treating with TPA for 36 hours.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] 加藤巌: "Cytolytic toxinの細胞膜受容体と膜障害作用" 最新医学. 43. 1213-1218 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 加藤巌: "細胞感染症成立に関与する菌体外酵素" 日本細胞菌学雑誌. 43. 621-628 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Iwao Kato,Naoko Morinaga and Reiko Muneto: "Non-thiol-activated cytolytic bacterial toxins;Current status." Microbiological Sciences. 5. 53-57 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Noko Morinaga,Mitiko nakamori and Iwao Kato: "Changes in binding of staphylococcal leukocidin to HL-60 cells during differentiation induced by dimethyl sulfoxide." Infect Immunology. 56. 2479-2483 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Iwao Kato and Masatoshi Noda: "ADP-ribosyflation of cell membrane proteins by staphylococcal α-toxin and leukocidin in rabbit erythrocytes and polymorphonuclear leukocytes." FEBS Lett.255. 59-62 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 加藤巌: "細菌性細胞溶解毒素生物トキシン:医学・生物学への応用(加藤巌編)" 学会出版センタ-(東京), 13 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masatoshi Noda and Iwao Kato: "Purification and crystallization of staphylococcal leukocidin.In;Methods in Enzymology(Harshman S ed)" Academic Press,New York, 11 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 加藤巌,内田驍: "ADP-リボシル化毒素と標的分子" 菜根出版(東京), 161 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kato, I., Morinaga, N., Muneto, R.: "Non-thiol-activated cytolytic bacterial toxins." Microbiol. Sci. 5(2), 53-57 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Morinaga, N., Nagamori, M., Kato, I.: "Changes in binding of staphylococcal leukocidin to HL-60 cells during differentiation induced by dimethyl sulfoxide." Infect. Immun. 56(9), 2479-2483 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kato, I., Noda, M.: "ADP-ribosylation of cell membrane proteins by staphylococcal alpha-toxin and leukocidin in rabbit erythrocytes and polymorphonuclear leukocytes." FEBS Letter 255(1) 59-62 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kato, I.: Biotoxins: Applications of medicine and biology.Gakukai Publishing Center, Tokyo, (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Noda, M., Kato, I.: Methods in Enzymology (Harshman, S. ed.), vol.165. Academic Press, New York, 22-32 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kato, I., Uchida, T.: ADP-ribosyl toxins and target molecules.Saikon Publishing Co.Ltd., Tokyo, (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kato,Iwao;Morinaga,Naoko;Muneto,Reiko: Microbiol.Sci.5. 53-57 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Morinaga,Naoko;Nagamori,Michiko;Kato,Iwao: Infect.Immun.56. 2479-2483 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 野田公俊、加藤巌: 日本細菌学雑誌. 44. 87 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 宮崎祐子,野田公俊、加藤巌: 日本細菌学雑誌. 44. 267 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 王夏、野田公俊、加藤巌: 日本細菌学雑誌. 44. 268 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 盛永直子、加藤巌、野田公俊: 日本細菌学雑誌. 44. 269 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 加藤巌 編: "生物トキシン-医学、生物学への応用" 株式会社学会出版センター, 1-227 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 加藤巌、内田驍 編: "ADPリボシル化毒素とその標識分子" 菜根出版, (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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