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Involvement of lipid radicals in new cell death ferroptosis

Research Project

Project/Area Number 18K19405
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKyushu University

Principal Investigator

Yamada Ken-ichi  九州大学, 薬学研究院, 教授 (60346806)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords脂質 / フェロトーシス / 薬学 / 細胞死 / スクリーニング
Outline of Final Research Achievements

In recent years, as a new cell death type, ferroptosis has been attracting attention, but the site of induction has been unclear. Therefore, in this study, we aimed to clarify whether lipid radicals were involved in the induction of ferroptosis. As a result, we found that lipid radicals were localized in the cell membrane and endoplasmic reticulum during induction of ferroptosis. Furthermore, we succeed to explain the difference in sensitivity of cells to ferroptosis.

Academic Significance and Societal Importance of the Research Achievements

フェロトーシスは、全く新しい細胞死形態であるため、その原因やメカニズムはほとんど分かっていない。本研究結果から、フェロトーシスの生成部位を明確にし、細胞間での感受性差も説明できる可能性を示した。このことは、新しい細胞死フェロトーシスの本質に迫っているのは間違いなく、「酸化脂質(脂質ラジカル)が単なる酸化副生成物ではなく、生体機能維持に極めて重要である」との新たな学理の発見とともに、創薬研究等への発展も期待できると考えている。

Report

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

    (33 results)

All 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (25 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers2019

    • Author(s)
      Mishima Eikan、Sato Emiko、Ito Junya、Yamada Ken-ichi、Suzuki Chitose、Oikawa Yoshitsugu、Matsuhashi Tetsuro、Kikuchi Koichi、Toyohara Takafumi、Suzuki Takehiro、Ito Sadayoshi、Nakagawa Kiyotaka、Abe Takaaki
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 31 Issue: 2 Pages: 280-296

    • DOI

      10.1681/asn.2019060570

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kinetics and localization of hemin-induced lipoprotein oxidation.2019

    • Author(s)
      Morales NP, Janprasit J, Ishida Y, Leuchapudiporn R,Yamada KI.
    • Journal Title

      Free Radic Res.

      Volume: 53:9-10 Issue: 9-10 Pages: 968-978

    • DOI

      10.1080/10715762.2019.1660323

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice†2019

    • Author(s)
      Ishii Naoki、Homma Takujiro、Lee Jaeyong、Mitsuhashi Hikaru、Yamada Ken-ichi、Kimura Naoko、Yamamoto Yorihiro、Fujii Junichi
    • Journal Title

      Biology of Reproduction

      Volume: 102 Pages: 102-115

    • DOI

      10.1093/biolre/ioz149

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation-Induced Redox Alteration in the Mouse Brain2019

    • Author(s)
      中村 美月,山﨑 俊栄,上野 恵美,柴田 さやか,尾澤 芳和,鎌田 正,中西 郁夫,山田 健一,青木 伊知男,松本 謙一郎
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 143 Pages: 412-421

    • DOI

      10.1016/j.freeradbiomed.2019.08.020

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ascorbic acid insufficiency impairs spatial memory formation in juvenile AKR1A-knockout mice2019

    • Author(s)
      Kurihara Kazuki、Homma Takujiro、Kobayashi Sho、Shichiri Mototada、Fujiwara Hiroki、Fujii Satoshi、Yamada Ken-ichi、Nakane Masaki、Kawamae Kaneyuki、Fujii Junichi
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 65 Issue: 3 Pages: 209-216

    • DOI

      10.3164/jcbn.19-41

    • NAID

      130007740759

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nitric Oxide Is Involved in Activation of Toll-Like Receptor 4 Signaling through Tyrosine Nitration of Src Homology Protein Tyrosine Phosphatase 2 in Murine Dextran Sulfate-Induced Colitis2018

    • Author(s)
      Tun X, Yasukawa K, Yamada KI
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 12 Pages: 1843-1852

    • DOI

      10.1248/bpb.b18-00558

    • NAID

      130007539535

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-12-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2-Oxo-histidine-containing dipeptides are functional oxidation products2018

    • Author(s)
      Ihara Hideshi、Kakihana Yuki、Yamakage Akane、Kai Kenji、Shibata Takahiro、Nishida Motohiro、Yamada Ken-ichi、Uchida Koji
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 4 Pages: 1279-1289

    • DOI

      10.1074/jbc.ra118.006111

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Inhibitory effects of several anti-oxidants toward lipid peroxidation2019

    • Author(s)
      Kota Saito, Yuta Matsuoka, Ken-ichi Yamada
    • Organizer
      SFRR-Asia 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂質由来アルデヒド化合物の構造同定と包括的解析法開発2019

    • Author(s)
      松岡悠太, 阿部雅史, 和泉自泰, 高橋政友, 馬場健史, 山田健一
    • Organizer
      第7回ケミカルバイオロジー学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A Method for the Structural Determination of Lipid-derived Radicals2019

    • Author(s)
      Yuta Matsuoka, Yoshihiro Izumi, Masatomo Takahashi, Takeshi Bamba, Ken-ichi Yamada
    • Organizer
      ICBL2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sample preparation procedure for oxidized phospholipids2019

    • Author(s)
      Masashi Abe, Yuta Matsuoka and Ken-ichi Yamada
    • Organizer
      ICBL2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibitory Effects of Several Antioxidants toward Lipid Peroxidation2019

    • Author(s)
      Kota Saito, Yuta Matsuoka, Ken-ichi Yamada
    • Organizer
      ICBL2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸化LDL 中脂質由来アルデヒドの体系的解析2019

    • Author(s)
      阿部 雅史, 松岡 悠太, 高橋 政友, 和泉 自泰, 馬場 健史, 山田 健一
    • Organizer
      第61回日本脂質生化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] リゾリン脂質アシル転移酵素はフェロトーシス誘導感受性に関与する2019

    • Author(s)
      日下部 大樹, 松岡 悠太, 山田 健一
    • Organizer
      第61回日本脂質生化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 酸化ストレス疾患に関与する酸化脂質の検出と抑制2019

    • Author(s)
      山田 健一
    • Organizer
      JADCI/JSHDR 2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] リン脂質脂肪酸組成の調節はフェロトーシス誘導剤の感受性を制御する2019

    • Author(s)
      日下部 大樹, 松岡 悠太, 山田 健一
    • Organizer
      第92回日本生化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質ラジカルの可視化と構造解析技術開発2019

    • Author(s)
      山田 健一
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 酸化LDL中酸化脂質の包括的解析2019

    • Author(s)
      阿部雅史, 松岡 悠太, 高橋 政友, 和泉 自泰, 馬場 健史, 山田 健一
    • Organizer
      第36回日本薬学会九州支部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質過酸化反応抑制剤は光誘発性網膜障害を抑制する2019

    • Author(s)
      石田南人, 城臺更, 進籐早紀, 松岡悠太, 山田健一
    • Organizer
      第36回日本薬学会九州支部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質ラジカル-ニトロキシドプローブ付加体精製法の開発2019

    • Author(s)
      齋藤 耕太, 松岡 悠太, 中尾 周平, どど 孝介, 袖岡 幹子, 山田 健一
    • Organizer
      第36回日本薬学会九州支部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 蛍光ニトロキシドプローブを用いた脂質ラジカル定量法の開発2019

    • Author(s)
      有働 拓海, 松岡 悠太, 高橋 政友, 和泉 自泰, 馬場 健史, 山田 健一
    • Organizer
      第36回日本薬学会九州支部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Detection and inhibition of in vivo lipid-derived radicals2019

    • Author(s)
      Ken-ichi Yamada
    • Organizer
      SfRBM2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lipid Radicals Cause Light Induced-Retinal Degeneration2019

    • Author(s)
      Ken-ichi Yamada
    • Organizer
      SFRRA+J 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂質ラジカルの検出・構造解析および抑制2019

    • Author(s)
      山田 健一
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] フェロトーシス誘導細胞における脂質過酸化反応の蛍光イメージング2019

    • Author(s)
      斎元 祐真, 日下部 大樹, 松岡 悠太, 山田 健一
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 光誘発性網膜障害における脂質過酸化反応抑制剤の網膜保護効果2019

    • Author(s)
      城臺更、石田南人、進藤早紀、日下部大樹、松岡悠太、山田健一
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂質膜内にて進行する脂質過酸化反応の機序解明2019

    • Author(s)
      中英人、松岡悠太、山田健一
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪酸添加はがん細胞のフェロトーシス感受性を亢進させる2019

    • Author(s)
      日下部 大樹, 松岡 悠太, 山田 健一
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂質ラジカル抑制剤探索に向けたスクリーニング系の構築とその応用2019

    • Author(s)
      進籐 早紀, 松岡 悠太, 山田 健一
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂質過酸化反応における抗酸化物質の作用点および反応抑制機序の解明2019

    • Author(s)
      齋藤 耕太, 松岡 悠太, 山田 健一
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 非アルコール性脂肪肝炎モデルへの脂質過酸化抑制剤の応用2018

    • Author(s)
      北島綾子, 日下部 大樹, 進藤 早紀, 松岡 悠太, 山田 健一
    • Organizer
      第35回日本薬学会九州支部大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂質過酸化反応を抑制する化合物の探索と両側総頸動脈狭窄モデルマウスへの応用2018

    • Author(s)
      宗 茉里恵, 進藤 早紀, 松岡 悠太, 山田 健一
    • Organizer
      第35回日本薬学会九州支部大会
    • Related Report
      2018 Research-status Report
  • [Book] 酸化脂質クオリティの可視化と疾患制御 医学のあゆみ Vol.269 No.132019

    • Author(s)
      山田 健一
    • Publisher
      医歯薬出版
    • Related Report
      2019 Annual Research Report

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Published: 2018-07-25   Modified: 2021-02-19  

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