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2005 Fiscal Year Final Research Report Summary

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
Keywordsperiodontopathic bacteria / A. ACTINOMYCETEMCOMITANS / exotoxin / CDT / monocyte-macrophage / apoptosis / glycosphingolipids / caspase
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.

  • Research Products

    (20 results)

All 2006 2005 2004

All Journal Article (19 results) Book (1 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
    • Total Pages
      6担当
    • Publisher
      医歯薬出版株式会社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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