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Exploration of enhancer of ABCB4 to enable treatment of liver injury in cholestasis and arteriosclerosis

Research Project

Project/Area Number 18K14918
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionKobe Pharmaceutical University (2019-2020)
Shiga University of Medical Science (2018)

Principal Investigator

IKEDA Yoshito  神戸薬科大学, 薬学部, 助教 (40736980)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsリン脂質 / 胆汁酸 / ABCトランスポーター / ABCB4
Outline of Final Research Achievements

Bile salts are associated with phospholipid, the main constituents of bile, in mixed micells. The association of bile salts and phospholipid protects hepatocytes from the cytotoxicity of bile salts. ABCB4, a member of the ATP binding cassette transporter family, is present in the canalicular membrane of hepatocytes, and plays an essential role in the secretion of phospholipids into bile. In this study, we searched enhancer of ABCB4-mediated phospholipid efflux, and tried elucidation of its mechanism. We showed that ABCB4-mediated phospholipid efflux was significantly stimulated by taurine-conjugated hyodeoxycholate using cultured cells and experimental animals. In addition, it is conceivable that the enhancing effect of taurine-conjugated hyodeoxycholate on the ABCB4-mediated phospholipid efflux may be due to the strong mixed micelle formation ability.

Academic Significance and Societal Importance of the Research Achievements

ABCB4が疎水性の高いリン脂質を親水的環境である胆汁中へと排出する分子機序の詳細については不明であった。これはHDLの形成に関与するABCA1など、他の脂質トランスポーターにおいても共通の問題点である。本研究によって、リン脂質との混合ミセル形成能が高いタウリン抱合型ヒオデオキシコール酸が、リン脂質の優れたアクセプター分子として作用することが示唆された。これらの知見が、ABCB4だけでなく、他の脂質トランスポーターの輸送機序解明にも役立ち、関連する疾患の治療薬開発につながることが期待される。

Report

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

    (13 results)

All 2020 2019 2018 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Mechanism of Taurohyodeoxycholate-induced Biliary Phospholipid Efflux ―Understanding the Function of the ABCB4 Enhancer for Developing Therapeutic Agents against Bile Salt-induced Liver Injury―2020

    • Author(s)
      Ikeda Yoshito
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 140 Issue: 11 Pages: 1329-1334

    • DOI

      10.1248/yakushi.20-00156

    • NAID

      130007933476

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2020-11-01
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Exploration of Enhancer of ABCB4–mediated Phospholipid Efflux for the Protection of Hepatocytes Against Bile Salts2020

    • Author(s)
      Ikeda Yoshito
    • Journal Title

      MEMBRANE

      Volume: 45 Issue: 4 Pages: 182-186

    • DOI

      10.5360/membrane.45.182

    • NAID

      130007881617

    • ISSN
      0385-1036, 1884-6440
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Mechanisms for Protection of Hepatocytes against Bile Salt Cytotoxicity2019

    • Author(s)
      Shin-ya Morita, Yoshito Ikeda, Tokuji Tsuji, Tomohiro Terada
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 4 Pages: 333-340

    • DOI

      10.1248/cpb.c18-01029

    • NAID

      130007621742

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-04-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancing effect of taurohyodeoxycholate on ABCB4-mediated phospholipid efflux2019

    • Author(s)
      Ikeda Yoshito、Morita Shin-ya、Hatano Ryo、Tsuji Tokuji、Terada Tomohiro
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 1864 Issue: 10 Pages: 1495-1502

    • DOI

      10.1016/j.bbalip.2019.06.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] タウロヒオデオキシコール酸が有する胆汁中リン脂質排出促進作用とその機序2020

    • Author(s)
      池田義人
    • Organizer
      第70回日本薬学会関西支部大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 胆汁酸毒性低減を指向する肝細胞膜リン脂質トランスポーター活性化因子の探索2020

    • Author(s)
      池田義人
    • Organizer
      膜シンポジウム2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] タウロヒオデオキシコール酸が有する胆汁中リン脂質排出促進作用とその機序2019

    • Author(s)
      池田義人、森田真也、波多野亮、辻 徳治、寺田智祐
    • Organizer
      第69回 日本薬学会関西支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 胆汁リン脂質排出促進作用による新規肝機能改善薬の探索2018

    • Author(s)
      池田義人、森田真也、波多野 亮、辻 徳治、寺田智祐
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ABCB4によるリン脂質排出を強力に促進する分子の探索2018

    • Author(s)
      池田義人、森田真也、波多野 亮、辻 徳治、寺田智祐
    • Organizer
      第12回次世代を担う若手医療薬科学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] タウロヒオデオキシコール酸によるリン脂質排出トランスポーターABCB4の活性化2018

    • Author(s)
      池田義人、森田真也、波多野 亮、辻 徳治、寺田智祐
    • Organizer
      第13回トランスポーター研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] タウロヒオデオキシコール酸によるABCB4リン脂質排出の促進2018

    • Author(s)
      池田義人、森田真也、辻 徳治、寺田智祐
    • Organizer
      第60回 日本脂質生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ABCB4リン脂質排出を促進する分子の探索とメカニズムの解明2018

    • Author(s)
      池田義人、森田真也、辻 徳治、寺田智祐
    • Organizer
      日本膜学会第40年会
    • Related Report
      2018 Research-status Report
  • [Remarks] 神戸薬科大学 医薬細胞生物学研究室

    • URL

      https://medicinalcellbiolo.wixsite.com/kpu-med-cell-biol

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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