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Molecular biological analysis of the exotoxin derived from periodontopathic bacteria on peridontal medicine

Research Project

Project/Area Number 16390615
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontal dentistry
Research InstitutionKyushu Dental College

Principal Investigator

NISHIHARA Tatsuji  Kyushu Dental College, Dentistry, Professor, 歯学部, 教授 (80192251)

Co-Investigator(Kenkyū-buntansha) YAMATO Kenji  Tokyo Medical and Dental University, Dentistry, Lecturer, 歯学部, 講師 (50174751)
AKIFUSA Sumio  Kyushu Dental College, Dentistry, Special Researcher, 歯学部, 特別研修員 (40295861)
TSUJISAWA Toshiyuki  Kyushu Dental College, Dentistry, Assistant, 歯学部, 助手 (60265006)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
Keywordsperiodontopathic bacteria / A. ACTINOMYCETEMCOMITANS / exotoxin / CDT / monocyte-macrophage / apoptosis / glycosphingolipids / caspase / 単球・リンパ系細胞
Research Abstract

Actinobacillus actinomycetemcomitans produces a toxin, called cytolethal distending toxin (CDT), which causes host cell DNA damage leading to the induction of DNA damage checkpoint pathways. CDT consists of three subunits, CdtA, CdtB, and CdtC CdtB is the active subunit of CDT and exerts its effect as a nuclease that damages nuclear DNA, triggering cell cycle arrest. In the present study, we confirmed that the only combination of toxin proteins causing cell cycle arrest was that of all three recombinant CDT (rCDT) protein subunits. Furthermore, in order for rCDT to demonstrate toxicity, it was necessary for CdtA and CdtC to access the cell before CdtB. The coexistence of CdtA and CdtC was necessary for these subunits to bind to the cell. Cells treated with the glucosylceramide synthesis inhibitor 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol showed resistance to the cytotoxicity induced by rCDT. Furthermore, LY-B cells, which are deficient in the biosynthesis of sphingolipid, also showed resistance to the cytotoxicity induced by rCDT. To evaluate the binding of each subunit for glucosylceramides, we performed thin-layer chromatography immunostaining. The results indicated that each subunit reacted with the GM1, GM2, GM3, Gb3, and Gb4. The rCDT mixture incubated with liposomes containing GM3 displayed partially reduced toxicity. These results indicate that GM3 can act as a CDT receptor.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (34 results)

All 2006 2005 2004

All Journal Article (31 results) Book (3 results)

  • [Journal Article] Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA.2006

    • Author(s)
      Yamato, K. et al.
    • Journal Title

      Cancer Gene Therapy 13

      Pages: 234-241

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells2005

    • Author(s)
      Kato, S. et al.
    • Journal Title

      J. Med. Microbiol. 54

      Pages: 293-298

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid2005

    • Author(s)
      Ariyoshi, W. et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 18967-18972

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of ganglioside GM3 in G2/M cell cycle arrest of human monocytic cells induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin2005

    • Author(s)
      Mise, K. et al.
    • Journal Title

      Infect. Immun. 73

      Pages: 4846-4852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enamel matrix derivative promotes osteoclast cell formation by RANKL production in mouse marrow cultures2005

    • Author(s)
      Otsuka, T. et al.
    • Journal Title

      J. Dentistry 33

      Pages: 749-755

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Actinobacillus actinomy- cetemcomitans induces apoptosis in human monocytic THP-1 cells2005

    • Author(s)
      Kato, S. et al.
    • Journal Title

      J. Med. Microbiol. 54

      Pages: 293-298

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid2005

    • Author(s)
      Ariyoshi, W. et al.
    • Journal Title

      J. Biol. Chem. 289

      Pages: 18967-18972

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of ganglioside GM3 in G2/M cell cycle arrest of human monocytic cells induced by Actinobacillus actinomycetem-comitans cytolethal distending toxin2005

    • Author(s)
      Mise, K. et al.
    • Journal Title

      Infect. Immun. 73

      Pages: 4846-4852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microbicidal efficacy of ozonated water against Candida albicans adhered to acetylic resin plate.2005

    • Author(s)
      Arita, M. et al.
    • Journal Title

      Oral Mictobiol. Immunol. 20

      Pages: 206-210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Platelet-rich plasma enhances human osteoblast-like cell proliferation and differentiation.2005

    • Author(s)
      Kanno, T. et al.
    • Journal Title

      J. Oral Maxillofac. Surg. 63

      Pages: 362-369

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thermotolerance of pulp cells and phagocytosis of apoptotic pulp cells by surviving pulp cells following heat stress.2005

    • Author(s)
      Kitamura, C. et al.
    • Journal Title

      J. Cell. Physiol. 94

      Pages: 826-834

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thermotolerance of pulp cells and phagocytosis of apoptotic pulp cells b surviving pulp cells following heat stress2005

    • Author(s)
      Kitamura, C.
    • Journal Title

      J.Cell.Physiol 94

      Pages: 826-834

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Actinobacillus actinomycetemcomitans induces apoptosis in human monocytis THP-1 cells2005

    • Author(s)
      Kato, S.
    • Journal Title

      J.Med.Microbiol. 54

      Pages: 293-298

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid2005

    • Author(s)
      Ariyoshi, W.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 18967-18972

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of ganglioside GM3 in G2/M cell cycle arrest of human monocytic cells induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin2005

    • Author(s)
      Mise, K.
    • Journal Title

      Infect.Immun. 73

      Pages: 4846-4852

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tensile mechanical strain up-regulates Runx2 and osteogenic factor expression in human periosteal cells : Implications for distraction osteogenesis2005

    • Author(s)
      Kanno, T.
    • Journal Title

      J.Oral and Maxillofacial surgery 63

      Pages: 499-504

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enamel matrix derivative promotes osteoclast cell formation by RANKL production in mouse marrow cultures2005

    • Author(s)
      Otsuka, T.
    • Journal Title

      J.Dentistry 33

      Pages: 749-755

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SC-19220, antagonist of prostaglandin E2 receptor EP1, inhibits osteoclastogenesis by RANKL.2005

    • Author(s)
      Tsujisawa, T. et al.
    • Journal Title

      J Bone and Mineral Res. 20

      Pages: 15-22

    • NAID

      110006420762

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Microbial etiology of periodontitis.2004

    • Author(s)
      Nishihara, T. et al.
    • Journal Title

      Periodontology 2000 36

      Pages: 14-26

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of caspase activation through release of cytochromec from mitochondria in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans.2004

    • Author(s)
      Kasai, H, et al.
    • Journal Title

      FEMS Microbiol. Lett. 233

      Pages: 29-35

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microbial etiology of periodontitis.2004

    • Author(s)
      Nishihara, T. et al.
    • Journal Title

      Periodontology 2000. 36

      Pages: 14-26

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of caspase activation through release of cytochrome c from mitochondria in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans2004

    • Author(s)
      Kasai, H, et al.
    • Journal Title

      FEMS Microbiol. Lett. 233

      Pages: 29-35

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanisms involved in apoptosis of human macrophages induces by lipopolysaccharide from Actinobacillus actinomy- cetemcomitans in the presence of cycloheximide.2004

    • Author(s)
      Suzuki, T. et al.
    • Journal Title

      Infect. Immun. 72

      Pages: 1856-1865

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] y-Interferon enhances expression of membrane CD14/MyD88 and subsequent responsiveness to lipopoly-saccharide from Actinobacillus actinomycetemcomitans in human gingival fibroblasts.2004

    • Author(s)
      Mochizuki, S. et al.
    • Journal Title

      J. Periodont. Res. 39

      Pages: 333-343

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Delivery of cytolethal distending toxin B induces cell cycle arrest and apoptosis in gingival squamous cell carcinoma in vitro.2004

    • Author(s)
      Yamamoto, K. et al.
    • Journal Title

      Eur. J. Oral Sci. 112

      Pages: 445-451

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antimicrobial effect of ozonated water on bacteria invading into dentinal tubules.2004

    • Author(s)
      Nagayoshi, M. et al.
    • Journal Title

      J. Endodontics 30

      Pages: 778-781

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Micrbial etiology of periodontitis.2004

    • Author(s)
      Nishihara, T. et al.
    • Journal Title

      Periodontol. 36

      Pages: 14-26

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of caspase activation through release of cytochrome c from mitochondria in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans.2004

    • Author(s)
      Kasai, H. et al.
    • Journal Title

      FEMS Microbiol.Lett. 233

      Pages: 29-35

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanisms involved in apoptosis of human macrophages induces by lipopolysaccharide from Actibacillus actinomycetemcomitans in the presence of cycloheximide.2004

    • Author(s)
      Suzuki, T. et al.
    • Journal Title

      Infect Immun. 72

      Pages: 1856-1865

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Antibacterial property of ozonated water against dental plaque biofilm.2004

    • Author(s)
      Nagayoshi, M. et al.
    • Journal Title

      Oral Microbiol.Immunol. 19

      Pages: 240-246

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells.2004

    • Author(s)
      Kat o, S. et al.
    • Journal Title

      J.Med.Microbiol. 54

      Pages: 1-6

    • Related Report
      2004 Annual Research Report
  • [Book] 看護で役立つ口腔乾燥と口腔ケア 機能低下の予防をめざして2005

    • Author(s)
      秋房住郎
    • Total Pages
      9
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2005 Annual Research Report
  • [Book] 歯周病と全身の健康を考える(財団法人ライオン歯科衛生研究所編)ドライマウスは歯周病にどのような影響を与えるのか2004

    • Author(s)
      西原達次
    • Publisher
      医歯薬出版株式会社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 歯周病と全身の健康を考える『ドライマウスは歯周病にどのような影響を与えるのか』( 財団法人ライオン歯科衛生研究所編)2004

    • Author(s)
      西原 達次
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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