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Synthesis of selenol-bearing membrane-bound antioxidative enzyme and its rescue effect from cell death due to the GPx-4 knockdown

Research Project

Project/Area Number 18K06617
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionSojo University

Principal Investigator

HARATAKE Mamoru  崇城大学, 薬学部, 教授 (40325668)

Co-Investigator(Kenkyū-buntansha) 中村 秀明  崇城大学, 薬学部, 講師 (30435151)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsセレノール / グルタチオンペルオキシダーゼ / セレン / 抗酸化酵素 / グルタチオンペルオキシダーぜ / 人工酵素 / リポソーム
Outline of Final Research Achievements

To obtain an effective glutathione peroxidase-4 (GPx-4) mimic under the physiological conditions, a lipid bilayer membrane-compatible selenenylsulfide derivative, 1-oxo-headecyl-seleno-L-cysteine-methyl-Se-yl-S-L-penicillamine methyl ester (OHSeP), was synthesized. The GPx-like catalytic activity of OHSeP in phosphatidylcholine (PC)-based colloidal liposomes was evaluated by the NADPH method using hydrogen peroxide as a substrate in physiological aqueous media. The OHSeP/PC liposomes preferably exerted in a GPx-like catalytic activity. A knockdown of the GPx-4 expression is lethal, since GPx-4 plays critical roles as a component of the antioxidant cell defense system. When siRNA-induced GPx-4 knockdown HepG2 cells were treated with the OHSeP/PC liposomes, the catalytic activity of OHSeP could successfully rescue from the cell death.

Academic Significance and Societal Importance of the Research Achievements

ヒトは進化の過程において,呼吸によって不可避に生じる過酸化物を消去するためにセレン原子を利用する強力な還元能を獲得している。しかし,セレン原子の特性は未だ医薬品へは応用されていない。本研究で得られた成果は,セレン原子の比類なき特性を活かした医薬品開発を進めるための基礎的知見となると考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (3 results)

  • [Journal Article] Peptidyl-prolyl cis-trans isomerase A participates in the selenium transport into the rat brain2021

    • Author(s)
      1.S. Yoshida, A. Yamamoto, H. Masumoto, T. Fuchigami, A. Toriba, M. Haratake, M. Nakayama
    • Journal Title

      Journal of Biological Inorganic Chemistry

      Volume: 26 Issue: 8 Pages: 933-945

    • DOI

      10.1007/s00775-021-01903-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acid-responsive HPMA copolymer-bradykinin conjugate enhances tumor-targeted delivery of nanomedicine2021

    • Author(s)
      2.E. Appiah, H. Nakamura, R. Pola, E. Grossmanova, O. Lidicky, A. Kuniyasu, T. Etrych, M. Haratake
    • Journal Title

      Journal of Controlled Release

      Volume: 337 Pages: 546-556

    • DOI

      10.1016/j.jconrel.2021.08.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Highly effective anti-tumor nanomedicines based on HPMA copolymer conjugates with pirarubicin prepared by controlled RAFT polymerization2020

    • Author(s)
      E. Randarova, H. Nakamura, R. Islam, M. Studenovsky, Mamoru Haratake, J. Fang, P. Chytil, T. Etrych
    • Journal Title

      Acta Biomaterialia

      Volume: 106 Pages: 256-266

    • DOI

      10.1016/j.actbio.2020.02.011

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Discovery of inner centromere protein-derived small peptides for cancer imaging and treatment targeting survivin.2020

    • Author(s)
      Fuchigami T, Ishikawa N, Nozaki I, Miyanari Y, Yoshida S, Yamauchi M, Soejima A, Haratake M, Nakayama M
    • Journal Title

      Cancer Sci

      Volume: 111(4) Issue: 4 Pages: 1357-1366

    • DOI

      10.1111/cas.14330

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 亜セレン酸還元代謝種と反応するラット脳由来タンパク質の同定2020

    • Author(s)
      吉田 さくら,山本 明典,増本 博司,堀 恵里子,浦 東子,淵上 剛志,原武 衛,中山 守雄
    • Organizer
      衛生薬学・環境トキシコロジー
    • Related Report
      2020 Research-status Report
  • [Presentation] Investigation of selenium absorption from selenotrisulfide compounds in cultured cells2020

    • Author(s)
      Sakura YOSHIDA, Ryosuke MORI, Risako HAYASHI, Takeshi FUCHIGAMI, Mamoru HARATAKE, Morio NAKAYAMA
    • Organizer
      金属の関与する生体関連反応シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] 血管透過性亢進ペプチドを用いた高分子性抗がん剤のがん組織集積増強法の検討2020

    • Author(s)
      Enoch APPIAH、Hideaki NAKAMURA, Robert POLA, Tomas ETRYCH, Mamoru HARATAKE
    • Organizer
      日本DDS学会学術集会
    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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