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Phylogenetic and biochemical approach for identifying the chronic proinflammatory proteins accumulated in protease-deficient species and individuals

Research Project

Project/Area Number 24592836
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNagasaki University

Principal Investigator

NISHISHITA Kazuhisa  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20237697)

Co-Investigator(Kenkyū-buntansha) SAKAI Eiko  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612)
OKAMOTO Kuniaki  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10311846)
TSUKUBA Takayuki  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
Research Collaborator FUKUMA Yutaka  
SUGAWARA Megumi  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsプロテアーゼ / 分子進化 / 偽遺伝子 / 細胞内プロテアーゼ / 免疫 / 感染 / 炎症
Outline of Final Research Achievements

We investigated the evolution and gene organization of the aspartic proteases, including cathepsin D, cathepsin E, pepsins, renin and napsins. Cathepsin E gene appears to be absent in Ruminants and Platypus. Human napsin B has been annotated as a pseudogene because it lacks an in-frame stop codon. napsin B orthologs are primarily distributed in primates, while napsin A orthologs are the only napsin genes in other species. Napsin B was duplicated from napsin A during the early stages of primate evolution, and the subsequent loss of napsin B function reflected ongoing human-specific napsin B pseudogenization.
Cathepsin E deficiency causes autophagy impairment concomitantly with increased aberrant mitochondria as well as increased oxidative stress in macrophage. The impaired adipose tissue development in high fat diet-fed cathepsin E-deficient mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (27 results)

All 2015 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (21 results)

  • [Journal Article] Kadowaki T, Kido MA, Hatakeyama J, Okamoto K, Tsukuba T, Yamamoto K. Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet.2014

    • Author(s)
      Kadowaki T, Kido MA, Hatakeyama J, Okamoto K, Tsukuba T, Yamamoto K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 446(1) Issue: 1 Pages: 212-217

    • DOI

      10.1016/j.bbrc.2014.02.089

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cathepsin E deficiency impairs autophagic proteolysis in macrophages.2013

    • Author(s)
      Tsukuba T, Yanagawa M, Kadowaki T, Takii R, Okamoto Y, Sakai E, Okamoto K, Yamamoto K
    • Journal Title

      PLos One

      Volume: 8(12) Issue: 12 Pages: e82415-e82415

    • DOI

      10.1371/journal.pone.0082415

    • NAID

      120006986749

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fisetin Inhibits Osteoclastogenesis Through Prevention of RANKL-Induced ROS Production by Nrf2-Mediated Up-regulation of Phase II Antioxidant Enzymes2013

    • Author(s)
      Y, Sakamoto H, Fumimoto R, Fukuma Y, Nishishita K, Okamoto K, and TsukubaT.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 121 Issue: 4 Pages: 288-298

    • DOI

      10.1254/jphs.12243FP

    • NAID

      10031171138

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural and phylogenetic comparison of napsin genes: the duplication, loss of function and human-specific pseudogenization of napsin B.2013

    • Author(s)
      Nishishita K, Sakai E, Okamoto K, Tsukuba T.
    • Journal Title

      Gene

      Volume: 517 Issue: 2 Pages: 147-57

    • DOI

      10.1016/j.gene.2013.01.013

    • NAID

      120006986226

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effects of tert-butylhydroquinone on osteoclast differentiation via up-regulation of heme oxygenase-1 and down-regulation of HMGB1 release and NFATc1 expression2013

    • Author(s)
      Yamaguchi Y, Sakai E, Sakamoto H, Fumimoto R, Fukuma Y, Nishishita K, Okamoto K, Tsukuba T.
    • Journal Title

      J Appl Toxicol

      Volume: (in press) Issue: 1 Pages: 0-0

    • DOI

      10.1002/jat.2827

    • Related Report
      2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deltamethrin inhibits osteoclast differentiation via regulation of heme oxygenase-1 and NFATc1.2012

    • Author(s)
      Sakamoto Hiroshi
    • Journal Title

      Toxicology in Vitro

      Volume: 26 Issue: 6 Pages: 817-822

    • DOI

      10.1016/j.tiv.2012.05.005

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] リクイリチゲニンの骨芽細胞および破骨細胞分化における影響2015

    • Author(s)
      岡元 邦彰,内野 加穂,米嶋 枝里香,坂井 詠子,西下 一久,筑波 隆幸
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] BMP 誘導骨芽細胞分化における転写因子 Transcription factor EB の役割2015

    • Author(s)
      米嶋 枝里香,岡元 邦彰,Xiaobin Wang,坂井 詠子,西下 一久,吉田 教明,筑波 隆幸
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-03-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Rab27Aは破骨細胞の多核化とリソソーム機能を制御する2014

    • Author(s)
      菅原めぐみ,坂井詠子,福間裕,西下一久,岡元邦彰,福田光則,泉哲郎,吉田教明,筑波隆幸
    • Organizer
      第87回日本生化学会大会合同大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nrf2遺伝子欠損マウスにおける酸化ストレスと骨代謝2014

    • Author(s)
      坂井詠子,山口優,福間裕,菅原めぐみ,西下一久,岡元邦彰,筑波隆幸
    • Organizer
      第87回日本生化学会大会合同大会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nrf2 遺伝子欠損マウスにおける酸化ストレスと破骨細胞分化2014

    • Author(s)
      坂井 詠子,福間 裕,菅原 めぐみ,西下 一久,岡元 邦彰,筑波 隆幸
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] コバルトプロトポルフィリンの破骨細胞分化および活性化に対する影響2014

    • Author(s)
      八島 由佳,岡元 邦彰,坂井 詠子,西下 一久,筑波 隆幸
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 破骨細胞の多核化とリソソーム機能を制御するrabタンパク質の同定2014

    • Author(s)
      菅原めぐみ,坂井詠子,福間裕,西下一久,岡元邦彰,吉田教明,筑波隆幸
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 破骨細胞の分化抑制に関するエラジタンニン類の作用メカニズムの解明2014

    • Author(s)
      岩竹 真弓,坂井 詠子,西下 一久,岡元 邦彰,筑波 隆幸
    • Organizer
      第56回歯科基礎医学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chemical constituents of Sanguisorba officinalis inhibits osteoclastogenesis.2014

    • Author(s)
      E. Sakai , M. Iwatake1, Y. Fukuma, K. Nishishita. K. Okamoto, T. Tanaka, and T. Tsukuba
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      東北大学(仙台市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Cobalt protoporphyrin prevents osteoclastogenesis via blocking of IkappaB phosphorylation2014

    • Author(s)
      八島 由佳、岡元 邦彰、坂井 詠子、西下 一久、筑波 隆幸
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      東北大学(仙台市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Chemical constituents from sanguisorba officinalis inhibits osteoclastogenesis.2013

    • Author(s)
      Sakai E, Iwatake M, Tanaka T, Tsukuba T
    • Organizer
      2nd International Conference on Pharma-Nutrition 2013
    • Place of Presentation
      シンガポール(シンガポール)
    • Related Report
      2013 Research-status Report
  • [Presentation] Inhibitory effects of a polyphenol from oak on bone diseases.2013

    • Author(s)
      Iwatake M, Sakai E, Tanaka T, Tsukuba T
    • Organizer
      2nd International Conference on Pharma-Nutrition 2013
    • Place of Presentation
      シンガポール(シンガポール)
    • Related Report
      2013 Research-status Report
  • [Presentation] Suppressive effects of an oak extract on osteoclast formation and bone resorption.2013

    • Author(s)
      Iwatake M, Sakai E, Okamoto K, Yoneshima E, Zaitsu Y, Tanaka T, Tsukuba T : Suppressive effects of an oak extract on osteoclast formation and bone resorption.
    • Organizer
      第86回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] リクイリチゲニンの破骨細胞形成への効果2013

    • Author(s)
      内野加穂,岡元邦彰,坂井詠子,福間裕,岩竹真弓,西下一久,筑波隆幸
    • Organizer
      第55回歯科基礎医学会学術大会
    • Place of Presentation
      岡山コンベンションセンター(岡山市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Sanguisorba officinalis由来化学成分の破骨細胞分化に対する影響,第55回歯科基礎医学会学術大会2013

    • Author(s)
      坂井詠子,岩竹真弓,西下一久,福間裕,岡元邦彰,筑波隆幸
    • Organizer
      第55回歯科基礎医学会学術大会
    • Place of Presentation
      岡山コンベンションセンター(岡山市)
    • Related Report
      2013 Research-status Report
  • [Presentation] カフェストールによる破骨細胞分化抑制作用2013

    • Author(s)
      福間裕, 坂井詠子, 菅原めぐみ, 西下一久, 岡元邦彰, 筑波隆幸
    • Organizer
      第66回日本薬理学会西南部会
    • Place of Presentation
      福岡大学(福岡市)
    • Related Report
      2013 Research-status Report
  • [Presentation] アスパラギン酸プロテアーゼナプシンの系統樹解析と生化学的解析-遺伝子重複、偽遺伝子化と機能喪失2013

    • Author(s)
      西下一久, 坂井詠子, 岡元邦彰, 筑波隆幸
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアホテル(神戸市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Fisetinの破骨細胞形成と骨吸収活性への影響

    • Author(s)
      坂井詠子,菅原めぐみ,福間裕,西下一久,岡元邦彰,筑波隆幸
    • Organizer
      第54回歯科基礎医学会学術大会
    • Place of Presentation
      福島
    • Related Report
      2012 Research-status Report
  • [Presentation] Cafestolの破骨細胞形成と骨吸収活性への影響

    • Author(s)
      福間裕,坂井詠子,菅原めぐみ,西下一久,岡元邦彰,筑波隆幸
    • Organizer
      第54回歯科基礎医学会学術大会
    • Place of Presentation
      福島
    • Related Report
      2012 Research-status Report
  • [Presentation] フィセチンはRANKLを介したROSの産生とNFATc1の発現を抑制することで破骨細胞分化を阻害する

    • Author(s)
      坂井詠子,菅原めぐみ,福間裕,西下一久,岩竹真弓,米嶋枝里香,岡元邦彰,筑波隆幸
    • Organizer
      第85回日本生化学会大会合同大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] p53はカテプシンE遺伝子の発現を制御する

    • Author(s)
      4. 岡元邦彰,岩田淳一,坂井詠子,西下一久,山本健二,筑波隆幸
    • Organizer
      第85回日本生化学会大会合同大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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