| Project/Area Number |
06454523
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
YAMAMOTO Kenji Kyushu University, Dentistry, Professor, 歯学部, 教授 (40091326)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Hiroshi Kyushu University, Dentistry, Research Associate, 歯学部, 助手 (20155774)
HORI Nobuaki Kyushu University, Dentistry, Associate Professor, 歯学部, 助教授 (60037520)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Porphyromonas gingivalis / periodontal pathogen / a virulence factor / Arg-gingipain / Lys-gingipain / cysteine proteinases / cloning / primary structures |
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| Research Abstract |
Progressive periodontal disease is characterized by acute progressive lesions of gingival connective tissue, excessive leukocyte infiltration, and occurrencr of a characteristic microflora. Porphyromonas gingivalis, a Gram-negative anaerobe, has been implicated in the etiology of the diease. The present study was undertaken to investigate the properties and functions of major periodontopathogenic proteinases from P.gingivalis. The results sre as follows : (1) We have identified two novel cysteine proteinases, termed Arg-gingipain and Lys-gingipain, in the culture supernatant of the organism, (2) the purified Arg-gingipain had the ability to gegrade collagens (types I and IV) and immunoglobulins G and A and to disrupt the functions of polymrophonuclear leukocytes, (3) we have isolated and sequenced the genes for both Arg-gingipain and Lys-gingipain. The predicted primary structures of both enzymes were found to be composed four funcional domains ; the N-terminal signal peptide required for the inner membrane transport, the N-terminal prosequence, which is assumed to stabilize the precursor structures, the proteinase domain, and the C-terminal hemagglutinin domain, which appears to be essential for extracellular secretion of the proteinase domains, (4) Arg-gingipain-deficient mutants have been constructed. The mutants showed loss of the proteolytic activity and of the inhibitory effect on polymorphonclear leukocyte functions. These findings clearly demonstrate that the proteinases produced by P.gingivalis make a significant contribution to the virulence of this organism.
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