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ROLES OF PATHOGENIC PROTEINASES IN PERIODONTAL DISEASE

Research Project

Project/Area Number 08407059
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

YAMAMOTO Kenji  KYUSHU UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY PROFESSOR, 歯学部, 教授 (40091326)

Co-Investigator(Kenkyū-buntansha) TSUKUBA Takayuki  KYUSHU UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY ASSISTANT PROFESSOR, 歯学部, 助手 (30264055)
NAKANISHI Hiroshi  KYUSHU UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY ASSISTANT PROFESSOR, 歯学部, 助手 (20155774)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 1998: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1997: ¥4,900,000 (Direct Cost: ¥4,900,000)
KeywordsPorphyromonas gingivalis / oral anaerobic bacterium / virulence factors / Arg-gingipain / Lys-gingipain / crysteine proteinase / periodontal disease / Porphyromonas gingivalis / 病原性プロテアーゼ / 病原性発現機序 / 病原菌プロテアーゼ / カテプシン
Research Abstract

The oral anaerobic bacterium Porphyromanas gingivalis has been implicated as a major etiologic agent of progressive periodontal disease. This bacterium produces a novel class of cysteine proteinases, now termed Arg-gingipain (RGP) and Lys-gingipain (KGP), that are responsible for the trypsine-like activity. In order to determine whether RGP and KGP are important for pathophysiology of the organism we have constructed RGP- and KGP-deficient mutants. The RGP-null mutant almost completely lost the inhibitory effect on chemiluminescence response of PMNs stimulated by serum-activated zymosan, suggesting that RGP is responsible for disruption of the bactericidal function of PMNs by P.gingivalis. The RGP-null mutant also showed a greater decrease of hemagglutination observed with the wild-type strain, suggesting that the rgp genes are involved in the hemagglutination activity of this organism. In addition, the RGP-null mutant showed little or no fimbriation. Since the precursors of fimbrilin and a 75-kDa protein underwent abnormal processing, RGP was shown to make a significant contribution to the virulence of P.gingivalis through processing of these cell surface proteins. On the other hand, the KGP-null mutant showed a greater decrease of the hemagglutination activity, but it retained the strong ability to disrupt the bactericidal activity of PMNs. More important, the KGP-null mutant-did not form black-pigmented colonies on blood agar plates, indicating its defect of hemoglobin adsorption and heme accumulation. These results strongly suggest that both RGP and KGP make a great contribution to the virulence of P.gingivalis through common and different mechanisms.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (71 results)

All Other

All Publications (71 results)

  • [Publications] Nakayama K., et al.: "Involvement of arginine-specific cysteine proteinase(Arg-gingipain)in fimbriation of Porphyromonas gingivalis." J.Bacteriol.178. 2812-2824 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okamoto K.,et al.: "Cloning and sequencing of the gene encoding a novel lysine-specific cysteine proteinase(Lys-gingipain)in Porphyromonas gingivalis:structural relationship with arginine-specific cysteine proteinase(Arg-gingipain)." J.Biochem. 120. 135-137 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kouzuma Y.,et al.: "Purification,characterization, and sequencing of two cysteine proteinase inhibitors,Sca and Scb,from the sunflower(Helianthus annuus)seeds." J.Biochem. 119. 1106-1113 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishishita K.,et al.: "Age-related and dexamethsone-induced changes in cathepsins E and D in rat thymic and splenic cells." Arch.Biochem.Biophys.333. 349-358 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kunimatsu K.,et al.: "Immunohistochemical study of cathepsin G and medullasin in inflamed gingival tissues from periodontal patients." J.Periodont.Res.32. 264-270 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama K.,et al.: "A hemoglobin receptor protein intragenetically encoded by the cysteine proteinaseencoding genes and the hemagglutinin-encoding gene of Porphyromonas gingivalis." Mol.Microbiol.27. 51-61 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe N.,et al.: "Biochemical and functional properties of lysine-specific cysteine proteinase(Lys-gingipain)as a virulence factor of Porphyromonas gingivalis." J.Biochem.123. 305-312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okamoto K.,et al.: "Involvement of a lysine-specific cysteine proteinase in hemoglobin adsorption and heme accumulation by Porphyromonas gingivalis." J.Biol.Chem.273. 21225-21231 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kadowaki T.,et al.: "Arg-gingipain acts as a major processing enzyme for various cell surface proteins in Porphyromonas gingivalis." J.Biol.Chem.273. 29072-29076 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sastradipura D.F.,et al.: "Identification of cellular compartments involved in processing of cathepsin E in primary cultures of rat microglia." J.Neurochem.75. 2045-2056 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama K., Yoshimura F., Kadowaki T., and Yamamoto K.: "Involvemnet of arginine-specific cysteine proteinase (Arg-gingipain) in fimbriation of Porphyromonas gingivalis." J.Bacteriol.178. 2812-2824 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okamoto K., Kadowaki T., Nakayama K.and Yamamoto K.: "Cloning and sequencing of the gene encoding a novel lysine-specific cysteine proteinase (Lys-gingipain) in Porphyromonas gingivalis : structural relationship with arginine-specific cysteine proteinase (Arg-gingipain)." J.Biochem. 120. 135-137 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kouzuma Y., Kawano K., Kimura M., Yamazaki N., Kadowaki T., and Yamamoto K.: "Purification, characterization, and sequencing of two cysteine proteinase inhibitors, Sca and Scb, from the sunflower (Helianthus annuus) seeds." J.Biochem. 119. 1106-1113 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishishita K., Sakai H., Sakai E., Kato Y., and Yamamot K.: "Age-related and dexamethsone-induced changes in cathepsins E and D in rat thymic and splenic cells." Arch.Biochem.Biophys.333. 349-358 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kunimatsu K., Ozaki Y., Hara Y., Aoki Y., Yamamoto K., and Kato I.: "Immunohistochemical study of cathepsin G and medullasin in inflamed gingival tissues from periodontal patients." J.Periodont.Res. 32. 264-270 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama K., Ratnayake D.B., Tsukuba T., Kadowaki T., Yamamoto K., and Fujimura S.: "A hemoglobin receptor protein intragenetically encoded by the cysteine proteinase-encoding genes and the hemagglutnin-encoding gene of Porphyromonas gingivalis." Mol.Microbiol. 27. 51-61 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe N., Kadowaki T., Okamoto K., Nakayama K., and Yamamoto K.: "Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis." J.Biochem. 123. 305-312 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okamoto K., Nakayama K., Kadowaki T., Abe N., Ratanayake D.B., and Yamamoto K.: "Involvement of a lysine-specific crysteine proteinase in hemoglobin adsorption and heme accumulation by Porphyromonas gingivalis." J.Biol.Chem. 273. 21225-21231 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kadowaki T., Nakayama K., Yoshimura F., Okamoto K., Abe N., and Yamamoto K.: "Arg-gingipain acts as a major processing enzyme for various cell surface proteins in Porphyromonas gingivalis." J.Biol.Chem.273. 29072-29076 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sastradipura D.F., Nakanishi H., Tsukuba T., Nishishita K., Sakai H., Kato Y., and Yamamoto K.: "Identification of cellular compartments involved in processing of cathepsin E in primary cultures of rat microglia." J.Neurochem. 75. 2045-2056 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama K.et al.: "A hemoglobin receptor protein intragenetically encoded by the cysteine proteinase-encoding genes and the hemagglutinin-encoding gene of Porphyromonas gingivalis." Mol.Microbiol. 27. 51-61 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe N.,et al.: "Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain)as a virulence factor of Porphyromonas gingivalis." J.Biochem.123. 305-312 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sastradipura D.F.,et al.: "Identification of cellular compartments involved in processing pf cathepsin E in primary cultures of rat microglia." J.Neurochem.75. 2045-2056 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda S.,et al.: "Rapid degradation of cathepsin E in pre-Golgi compartments after tunicamycin treatment." Dentistry in Japan. 34. 41-43 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okamoto K.,et al.: "Involvement of a lysine-specific cysteine proteinase in hemoglobin adsorption and heme accumulation by Po rphyromas gingivalis." J.Biol.CHem.273. 21225-21231 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kadowaki T.,et al: "Arg-gingipain acts as a major processing enzyme for various cell surface proteins in Porphyromonas gingivalis." J.Biol.Chem.273. 29072-29076 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto,Y.,et al.: "Expression of NMDA-receptor dependent long-term potential in the neostriatal neurons in an in vitro slice after ethanol withdrawal of the rat." Neuroscience. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukuda,T.et al.: "Novel non-apoptotic morphological changes in neurons of the mouse hippocampus following transient hypoxic-ischemia." Neurosci. Res.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,H.-D.et al.: "Differential effect of Bcl-2 overexpression on hippocampal CAI neurons and dentate granule cells following hypoxic-ischemia in the adult mice." J.Neurosci.Res.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takai, N.et al.: "Involvement of caspase-like proteinases in apoptosis of neuronal PC12 cells and primary cultured microglia induced by 6-hydroxydopamine." J.Neurosci.Res.54. 214-222 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tominaga,K.et al.: "Excitotoxin-induced neuronal death is associated with reponse of an unique intracellular aspartic proteinase cathepsin E." J.Neurichem.71. 2574-2584 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakanishi,H.et al.: "Hyperexcitability of amygdala neurons of senescence-accelerated mouse P10 revealed by electrophysiological and optical recordings in an in viro slice preparation." Brain Research. 812. 142-149 ( 1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山本健二,その他: "歯周病原性細菌Porphyromonas gingicaliが産生するシステインプロテアーゼの機能" 炎症. 18. 259-264 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中西博,山本健二: "神経細胞およびミクログリアのプロテアーゼを介したニューロン死の制御" 日本薬理学雑誌. 112. 77-78 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 右田啓介,その他: "バソプレシンによる最後野から弧束核への神経調節" 日本薬理学. 112. 148-152 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naknishi H.,and Yamamoto K.: "Cathepsin E in the central nervous system.Aspartic Proteinases(Ed:James M.N.G.)" Plenum Press,New York, 213-217 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakanishi H.et al.: "Increased expression of cathepsins E and D in neurons of aged rat brain and their colocalization with lipofuscin and carboxy-terminal fragments of Alzheimer amyloid precursor protein" J.Neurochem.68. 739-749 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakanishi H.et al.: "Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion" Neuroscience. 77. 1021-1028 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kunimatsu K.et al.: "Immunohistochemical study on cathepsin G and medullasin in inflamed gingival tissues from periodontal patinets" J.Periodont.Res.32. 264-270 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okamura K.et al.: "Immunohistochemical localization of cathepsin D,proliferating cell nuclear antigen and epidamal growth factor receptor in human breast carcinoma analyzed by computer image analyzer" Histopathol.31. 540-548 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 筑波隆幸 外: "新生タンパク質の品質管理機構" 日本薬理学雑誌. 109. 243-243 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 江頭 亨 外: "老化マーカーの検索とその制御" 日本薬理学雑誌. 110. 136-138 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山本健二外: "プロテオリシス-蛋白質分解の分解機構とバイオロジー" 蛋白質・核酸・酵素. 42. 2425-2432 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakayama K.et al.: "Hemoglobin receptor protein is intragenetically encoded by the cysteine proteinase-encoding genes and the haemagglutinin-encoding gene of Porphyromonas gingivalis" Mol.Microbiol.27. 51-61 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Abe N.et al.: "Biochemical and functional properties of lysine-specific cysteine proteinase(Lys-gingipain)as a virulence factor of Porphyromonas gingivalis in periodontal disease" J.Biochem.123. 305-312 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] sastradipura DF.et al.: "Identification of cellular compartments involved in processing of cathepsin E in primary cultures of rat microglia" J.Neurochem.70(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto K.et al.: "Medical Aspects of Proteases and Protease Inhibitors" IOS Press (Katunuma N,Kido H,Fritz H,Travis J.eds.), 629 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakai H.et al.: "Proteolysis in Cell Functions" IOS Press (Hopsu-Have VK,Javinen M,Kirschke H,eds.), 576 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okamoto K.et al.: "Proteolysis in Cell Functions" IOS Press (Hopsu-Have VK,Javinen M,Kirschke H,eds.), 576 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto K.et al.: "Proteolysis in Cell Functions" IOS Press (Hopsu-Have VK,Javinen M,Kirschke H,eds.), 576 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukuba T.et al.: "Proteolysis in Cell Functions" IOS Press (Hopsu-Have VK,Javinen M,Kirschke H,eds.), 576 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 山本健二 外: "ノックアウトマウスデータブック" 中山書店, 564 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukuba T.t et al.: "Biochemical properties of the monomeric mutant of human cathepsin E expressed in Chinese hamster ovary cells:Comparison with dimeric forms of the natural and ecombinant cathepsin E." J. Biochem.119. 126-134 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuo K., et al.: "Immunohistochemical localization of cathepsins D and E in human gastric cancer.A possible correlation with local invasive and metastatic activities of carcinoma cells." Human Pathol.27. 184-190 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kouzuma Y.,et al.: "Purification,characterization,and sequencing of two cysteine proteinase inhibitors,Sca and Scb,from Sunflower(Helianthus annuus)." J.Biochem.119. 1106-1113 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakayama K.,et al.: "Involvement of arginie-specific proteinsase(Arg-gingipain)in fimbriation of Porphyromonas gingivalis." J.Bacteriol.178. 2818-2824 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Azuma T.,et al.: "Expression of cathepsin E in pancrease:A possible tumor marker for pancreas,a preliminary report." Int. J. Cancer. 67. 492-497 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okamoto K.,et al.: "Cloning and sequencing of the gene encoding a novel lysine-specific cysteine proteinase(Lys-gingipain)in Porphyromonas gingivalis:Structural relationship with arginine-specific cysteine proteinase(Arg-gingipain)." J. Biochem.120. 398-406 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishishita K.,et al.: "Age-related and dexamethasone-induced changes in cathepsins E and D in rat thymic and splenic cells." Arch.Biochem.Biophys.333. 349-358 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakanishi H.,et al.: "Protective effect of MK-801 on the anoxia-aglycemia induced damage in the fluorocitrate-treated hippocampal slice of the rat." Brain Res.732. 232-236 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 山本健二: "プロテアーゼとプロテアーゼインヒビターの新しい機能.創薬研究の新展開を目指して" 日本薬理学会誌. 108. 135-137 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakanishi H.,et al.: "Increased expression of cathepsins E and D in neurons of the aged rat barin and their colocalization with lipofuscin and carboxy-terminal fragmnets of Alzheimer amyloid precursor protein." J. Neurochem.68. 739-749 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kunimats K.,et al.: "Immunohistochemical study of cathepsin G and medullasin in inflamed gingival tissues from periodontal patients." J.Periodont.Res.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakanishi H.,et al.: "Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occulsion." Neuroscience. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto K.,et al.: "Intracellular Protein Catabolism" Plenum Press(New York), 306 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 山本健二 他: "Modern Physician" 新興出版社, 24 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto K.,et al.: "Medical Aspects of Proteases and Protease Inhibitors" IOS Press(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto K.,et al.: "Proteolysis and Protein Turnover" IOS Press(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsukuba T.: "Medical Aspects of Proteases and Protease Inhibitors" IOS Press(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakai H.,et al.: "Proteolysis and Protein Turnover" IOS Press(in press), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okamoto K.,et al.: "Proteolysis and Protein Turnover" IOS Press(in press), (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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