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新規好中球活性化ペプチド、マイトクリプタイド-1の生理的機能の解明に関する研究

Research Project

Project/Area Number 16J11227
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Biomolecular chemistry
Research InstitutionNagahama Institute of Bio-Science and Technology

Principal Investigator

服部 竜弥  長浜バイオ大学, バイオサイエンス研究科, 特別研究員(PD)

Project Period (FY) 2016-04-22 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥700,000 (Direct Cost: ¥700,000)
Keywordsmitocryptide / 好中球 / 自然免疫 / マイトクリプタイド / 肝傷害モデルマウス
Outline of Annual Research Achievements

平成29年度において、ミトコンドリアタンパク質の配列中に隠された内因性の好中球活性化ペプチド、mitocryptide-1(MCT-1)の生理的な機能や存在意義について検討することを試みた。MCT-1は正常なブタ心臓組織より最初に単離・同定された好中球活性化ペプチドであり、組織中の存在量が最も多いmitocryptideであると考えられる。MCT-1に対する特異的中和モノクローナル抗体を予め投与した肝傷害モデルマウスと、vehicle (PBS)を投与したコントロールマウスを比較すると、MCT-1に対する中和抗体を投与したマウスにおいて傷害部位への好中球の浸潤は有意に阻害された。しかし、このMCT-1の中和抗体による傷害部位への好中球の浸潤阻害は部分的であり、完全には阻害しなかった。我々はまた、動物組織から同定しているMCT-1やmitocryptide-2 (MCT-2)以外にも、タンパク質情報データベースを利用し、ミトコンドリアタンパク質由来の高い好中球活性化能を有する50種類以上のペプチド配列を活性ペプチドとして同定している。そのうちのmitocryptide-3 (MCT-3)に対する特異的モノクローナル抗体を作製し、ヒト培養細胞由来のミトコンドリア破砕サンプルについてHPLCにより分取した画分について、抗MCT-3抗体による免疫活性を測定した。その結果、ヒトミトコンドリア中に抗MCT-3抗体に結合する分子が存在することを明らかなった。これらの研究成果は、多数のミトコンドリアタンパク質由来の好中球活性化ペプチドが自然免疫を制御する可能性を議論することに大きな意味を持つ。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (16 results)

All 2018 2017 2016

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Possible Existence of N-Formylated Peptides Derived from Cytochrome C Oxidase Subunit I2018

    • Author(s)
      Toshihiro Shimizu, Tatsuya Hattori, Takayuki Marutani, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Peptide Science

      Volume: 2017 Pages: 74-75

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitocryptide-2: Ligand Recognition Mechanisms of Formyl-Peptide Receptor 1 and Its Homologue Formyl-Peptide receptor 22018

    • Author(s)
      Kodai Nishino, Takayuki Marutani, Tatsuya Hattori, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Peptide Science

      Volume: 2017 Pages: 114-115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitocryptide-1: Investigation of Pathophysiological Roles of Mitocryptide-1 Utilizing Its Specific Neutralizing Monoclonal Antibody2018

    • Author(s)
      Hiroki Morikawa, Tatsuya Hattori, Yoshito Takamuro, Takayuki Marutani, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Peptide Science

      Volume: 2017 Pages: 142-143

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of monoclonal antibodies against mitocryptide-2: toward a new strategy to investigate the biological roles of cryptides2017

    • Author(s)
      Tatsuya Hattori, Takenori Yamada, Hiroki Morikawa, Takayuki Marutani, Koki Tsutsumi, Kodai Nishino, Toshihiro Shimizu, Yoshisuke Nishi, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Journal of Peptide Science

      Volume: 23 Issue: 7-8 Pages: 610-617

    • DOI

      10.1002/psc.3000

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-activity relationships of mitocryptide-2 for the elucidation of ligand recognition mechanisms of formyl-peptide receptor 22017

    • Author(s)
      Kodai Nishino, Takayuki Marutani, Koki Tsutsumi, Tatsuya Hattori, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Peptide Science

      Volume: 2016 Pages: 107-108

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acquisition of specific monoclonal antibody against mitocryptide-2 for the detection of early stage of inflammation2017

    • Author(s)
      Takenori Yamada, Tatsuya Hattori, Akane Fukui, Takayuki Marutani, Koki Tsutsumi, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Peptide Science

      Volume: 2016 Pages: 119-120

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preparation of specific neutralizing monoclonal antibody against mitocryptide-3 for the elucidation of its physiological roles2017

    • Author(s)
      Hiroki Morikawa, Tatsuya Hattori, Kenta Nakashima, Takayuki Marutani, Koki Tsutsumi, Yoshiaki Kiso, Hidehito Mukai
    • Journal Title

      Peptide Science

      Volume: 2016 Pages: 155-156

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial protein-derived cryptides: are endogenous N-formylated peptides including mitocryptide-2 components of mitochondrial damage-associated molecular patterns?2016

    • Author(s)
      Marutani, T., Hattori, T., Tsutsumi, K., Koike, Y., Harada, A., Noguchi, K., Kiso, Y., and Mukai, H.
    • Journal Title

      Biopolymers: Peptide Science

      Volume: 106 Issue: 4 Pages: 580-587

    • DOI

      10.1002/bip.22788

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Possible Existence of N-Formylated Peptides Derived from Cytochrome C Oxidase Subunit I2017

    • Author(s)
      Toshihiro Shimizu, Tatsuya Hattori, Takayuki Marutani, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mitocryptide-2: Ligand Recognition Mechanisms of Formyl-Peptide Receptor 1 and Its Homologue Formyl-Peptide receptor 22017

    • Author(s)
      Kodai Nishino, Takayuki Marutani, Tatsuya Hattori, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mitocryptide-1: Investigation of Pathophysiological Roles of Mitocryptide-1 Utilizing Its Specific Neutralizing Monoclonal Antibody2017

    • Author(s)
      Hiroki Morikawa, Tatsuya Hattori, Yoshito Takamuro, Takayuki Marutani, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Structure-activity relationships of mitocryptide-2 for the elucidation of ligand recognition mechanisms of formyl-peptide receptor 22016

    • Author(s)
      Kodai Nishino, Takayuki Marutani, Koki Tsutsumi, Tatsuya Hattori, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都 TERRSA(京都府・京都市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Acquisition of specific monoclonal antibody against mitocryptide-2 for the detection of early stage of inflammation2016

    • Author(s)
      Takenori Yamada, Tatsuya Hattori, Akane Fukui, Takayuki Marutani, Koki Tsutsumi, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都 TERRSA(京都府・京都市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Preparation of specific neutralizing monoclonal antibody against mitocryptide-3 for the elucidation of its physiological roles2016

    • Author(s)
      Hiroki Morikawa, Tatsuya Hattori, Kenta Nakashima, Takayuki Marutani, Koki Tsutsumi, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都 TERRSA(京都府・京都市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリアDAMPsの活性候補因子であるマイトクリプタイドが惹起する好中球遊走メカニズムの解析2016

    • Author(s)
      服部竜弥、森川広樹、堤光己、丸谷飛之、木曽良明、向井秀仁
    • Organizer
      第89回 日本生化学会大会
    • Place of Presentation
      仙台国際センター/東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mitocryptides induce neutrophil migration in vivo as mitochondrial DAMPs promote2016

    • Author(s)
      Tatsuya Hattori, Hiroki Morikawa, Koki Tsutsumi, Takayuki Marutani, Yoshiaki Kiso, Hidehito Mukai
    • Organizer
      34th European Peptide Symposium / 8th International Peptide Symposium
    • Place of Presentation
      Leipzig University (Leipzig, Germany)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-05-17   Modified: 2024-03-26  

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