• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

歯周病原菌における蛋白分解システムとその異常の分子レベル解析

Research Project

Project/Area Number 09877353
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionKyushu University

Principal Investigator

山本 健二  九州大学, 歯学部, 教授 (40091326)

Co-Investigator(Kenkyū-buntansha) 中西 博  九州大学, 歯学部, 助手 (20155774)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsArg-gingipain / Lys-gingipain / システインプロテアーゼ / 歯周病原性プロテアーゼ / 蛋白分解システム / 酵素欠損変異体 / Prophyromonas gingivalis / グラム陰性嫌気性細菌 / Porphyromonas gingivalis
Research Abstract

歯周病の主要な病原性細菌の一つであるPorphyromonasginglvalisには細胞結合型および細胞外分泌型のさまざまなプロテアーゼが存在しており、本菌の重要な生理機能や病原性機能を担っていると考えられている。筆者らはこれまで本菌が産生する主要なプロテアーゼとして2つのユニークなシステインプロテアーゼ(ペプチド結合の切断の特異性からアルギニン特異的システインプロテアーゼArg-gingipain(RGP)およびリジン特異的システインプロテアーゼLys-gingipain(KGP)と呼んでいる)の生化学的ならびに遺伝学解析を通じて両酵素が本菌の病原性発現に必須の因子であることを明らかにしてきた。本年度は、RGPをコードする2つの遺伝子とKGPをコードする遺伝子の両方を同時欠損させた三重変異株を作成し、野生株ならびに前年度に作成したそれぞれの酵素の単一完全欠損株のもつ様々な機能に及ぼす影響を調べた。その結果、三重欠損株では細胞内にも細胞外にもまったくRGPおよびKGPの活性は認められず、タイプIコラーゲンや免疫グロブリンなどの分解活性も検出されなかった。さらに、この変異株は牛血清アルブミンのみを含む栄養培地では生育することができなかった。これらの結果から、RGPおよびKGPは栄養源やエネルギー源として利用するアミノ酸の産土や菌体内への取込みに必須であることが明らかにされた。一方筆者らは、前縁度の研究からrgpAおよびkgp遺伝子のC末端領域とヘムアグルチニン遺伝子hagAには本菌の血球凝集素活性やヘモグロビン結合に必要な接着ドメインが存在していることを明らかにしているが、本研究ではrgpA・kgp・hagA欠損三重変異株を作成して野生株のもつ血球凝集素活性やヘモグロビン結合活性に及ぼす影響を調べた。その結果、この変異株では血球凝集素活性もヘモグロビン結合活性もなく、これらの遺伝子産物が本菌の血球凝集能やヘモグロビン結合能に大きく貢献していることが示された。

Report

(2 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Nakayama K.et al.: "A hemoglobin receptor protein intragenetically encoded by the cysteine proteinase-encoding genes and the hemagglutinin-encoding gene of Prophyromonas 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 of 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 tunicamcin 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 Prophyromas 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] 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 response of an unique intracellular aspartic proteinase cathepsin E." J.Neurochem.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 vitro 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 gingivalis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: "神経脂肪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." 日本薬理学会雑誌. 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" 日本薬理学雑誌. 112. 148-152 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto,Y.et al.: "Expression of NMDA-receptor dependent long-term potentiation 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 followin 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 CA1 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] Nakanishi 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

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi