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Analysis for cell-penetrating mechanism of histidine-rich peptide/proteins

Research Project

Project/Area Number 17K07771
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bioorganic chemistry
Research InstitutionTottori University

Principal Investigator

Iwasaki Takashi  鳥取大学, 農学部, 准教授 (30585584)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsヒスチジン / 細胞膜透過 / トランスサイトーシス / 細胞毒性 / 病原性因子 / ピロリ菌 / マラリア / タンパク質 / ペプチド / 蛋白質 / 細胞
Outline of Final Research Achievements

Previously, we found that synthesized histidine-rich peptide/proteins are efficiently internalized into mammalian cells. This finding suggests the possibility that natural histidine-rich peptide/proteins also show cellular uptake.
In this study, we focused on histidine-rich peptide (Hpn) and histidine-rich protein Ⅱ (HRP2) derived from Helicobacter pylori and Plasmodium falciparum, respectively. The Hpn has been known to form amyloid-like oligomer and thought as a pathogenicity factor for Alzheimer's disease. Interestingly, here, the Hpn showed cellular uptake and transcytosis in the human gastric epithelial tumor cells. On the other hand, the HRP2 also showed cellular uptake in various human cell lines and cytotoxic effects on human fibrosarcoma. These findings suggest a possibility that the Hpn and HRP2 play as a pathogenic factor in the human body.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ピロリ菌HpnとマラリアHRP2が細胞内に取り込まれた後に、病原性因子として機能する可能性を明らかにした。これらのヒスチジンリッチペプチド/タンパク質を標的分子として考えることで、ピロリ菌やマラリア原虫感染症に対する新たな治療方針を開拓することができる。また、ピロリ菌HpnやマラリアHRP2以外の天然のヒスチジンリッチペプチド/タンパク質についても、同様に細胞内に取り込まれる可能性を示唆することができた。今後は、他種のヒスチジンリッチペプチド/タンパク質についてさらなる調査をすることで、新たな現象の発見につながることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Development of Organelle Replacement Therapy Using a Stearyl-Polyhistidine Peptide against Lysosomal Storage Disease Cells2019

    • Author(s)
      T. Hayashi, R. Okamoto, T. Kawano, T. Iwasaki
    • Journal Title

      Molecules

      Volume: 24 Issue: 16 Pages: 2995-2995

    • DOI

      10.3390/molecules24162995

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug delivery using polyhistidine peptide-modified liposomes that target endogenous lysosome2018

    • Author(s)
      T. Hayashi, M. Shinagawa, T. Kawano, T. Iwasaki
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 501 Issue: 3 Pages: 648-653

    • DOI

      10.1016/j.bbrc.2018.05.037

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of physiological functions of antagonistic insulin-like peptides, INS-23 and INS-18, in Caenorhabditis elegans2018

    • Author(s)
      Y. Matsunaga, T. Matsukawa, T. Iwasaki, K. Nagata, T. Kawano
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 82 Issue: 1 Pages: 90-96

    • DOI

      10.1080/09168451.2017.1415749

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Helicobacter pylori由来ヒスチジンリッチペプチドの生理機能解析2019

    • Author(s)
      乾由莉香、河野 強、岩﨑 崇
    • Organizer
      第51回若手ペプチド夏の勉強会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Transcytosis of histidine-rich peptide derived from Helicobacter pylori in gastric epithelial cells2019

    • Author(s)
      Y. Inui, T. Kawano, T. Iwasaki
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Histidine-rich protein: a new pathogenic factor of Plasmodium falciparum malaria2019

    • Author(s)
      M. Shimoda, T. Kawano, T. Iwasaki
    • Organizer
      AFELiSA 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マラリア原虫ヒスチジンリッチタンパク質 (PfHRP2) の細胞膜透過と細胞毒性に関する研究2019

    • Author(s)
      下田麻由、河野 強、岩﨑 崇
    • Organizer
      2019年度日本農芸化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Malaria Histidine-Rich Protein Shows Cell Penetration and Cytotoxicity2018

    • Author(s)
      M. Shimoda, T. Kawano, T. Iwasaki
    • Organizer
      AFELiSA 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Cell-Penetrating Peptides as Molecular Delivery Carriers for Human Health and Plant Breeding2018

    • Author(s)
      T. Iwasaki
    • Organizer
      AFELiSA 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞膜透過ペプチド『ポリヒスチジン』の薬物輸送キャリアーとしての機能評価2017

    • Author(s)
      岩崎 崇・徳田佳久・小竹彩香・笹原駿介・河野 強
    • Organizer
      第12回ケミカルバイオロジー学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞膜透過ペプチド『ポリヒスチジン』の発見と動物・植物細胞に対する応用研究2017

    • Author(s)
      岩崎 崇
    • Organizer
      日本農芸化学会中四国支部 第26回若手研究者シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] ペプチド医薬品のスクリーニング・安定化・製剤化技術2017

    • Author(s)
      技術情報協会 企画編集
    • Total Pages
      557
    • Publisher
      技術情報協会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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