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Elucidation of physiological roles of fatty acyl species of late endosome-specific phospholipid BMP

Research Project

Project/Area Number 18K16246
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionJuntendo University

Principal Investigator

LEE-OKADA Hyeon-Cheol  順天堂大学, 医学部, 助教 (30758321)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsBMP / DHA / DPA / PUFA / 後期エンドソーム / 脂肪酸組成 / 高度不飽和脂肪酸 / ドコサヘキサエン酸
Outline of Final Research Achievements

BMP is an enigmatic phospholipid that is specifically localized in intralumenal vesicles of late endosomes, and is thought to be essential for proper functions of late endosomes. BMP has a propensity to incorporate polyunsaturated fatty acids (PUFAs). However, the physiological meaning of PUFA-containing BMP fatty acyl species is unknown. We created a knockout mouse line that showed reduced levels of PUFA-containing BMP, and found that they had increase levels of oxidative stress markers. We also found that these mice were susceptible to reagents that cause oxidative stress. These data taken together suggest that BMP efficiently incorporates labile PUFAs to avoid oxidative environment within the cells.

Academic Significance and Societal Importance of the Research Achievements

様々な疾患や病態に対し、予防・治療効果を示すオメガ3脂肪酸は、サプリメントとしても人気のある重要な栄養素の一つである。オメガ3脂肪酸は分子内に不飽和結合を多数有するため、非常に酸化されやすい性質を有しているが、生体がどのようにオメガ3脂肪酸の酸化を防いでいるか不明であった。本研究は細胞内へ取り込まれたオメガ3脂肪酸がどのように酸化から守られているか説明する分子機構の一端を明らかにする研究であり、本研究を継続しオメガ3脂肪酸の細胞内動態をより詳細に解析することにより、オメガ3脂肪酸をより効率よく摂取する方法論の開発へと繋げたいと考えている。

Report

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

    (10 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Sensitization of Gastric Cancer Cells to Irinotecan by p53 Activation2019

    • Author(s)
      Zhang Shun、Kohira Yoshinori、Orita Hajime、Ishimine Momoko、Kobayashi Toshiyuki、Buendia Chua Sharlyn Mae、Nakaoka Hirofumi、Inoue Ituro、Hino Okio、Yokomizo Takehiko、Fukunaga Tetsu、Lee-Okada Hyeon-Cheol
    • Journal Title

      BPB Reports

      Volume: 2 Pages: 130-133

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dietary supplementation of omega-3 fatty acid eicosapentaenoic acid does not ameliorate pruritus in murine models of atopic dermatitis and psoriasis.2019

    • Author(s)
      Lee H. C., Tominaga M., Yasukawa K., Ohba M., Takahashi N., Honda K., Okuno T., Takamori K., Yokomizo T.
    • Journal Title

      J Dermatol Sci

      Volume: 95 Issue: 3 Pages: 130-133

    • DOI

      10.1016/j.jdermsci.2019.07.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dietary omega-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.2019

    • Author(s)
      Hirakata T., Lee H. C., Ohba M., Saeki K., Okuno T., Murakami A., Matsuda A., Yokomizo T.
    • Journal Title

      FASEB J

      Volume: 33 Issue: 3 Pages: 3392-3403

    • DOI

      10.1096/fj.201801805r

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipid-metabolizing serine hydrolases in the mammalian central nervous system: endocannabinoids and beyond2018

    • Author(s)
      Shin Myungsun、Ware Timothy B.、Lee Hyeon-Cheol、Hsu Ku-Lung
    • Journal Title

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

      Volume: 1864 Issue: 6 Pages: 907-921

    • DOI

      10.1016/j.bbalip.2018.08.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 【生理活性脂質とアレルギー炎症】 脂肪酸由来の脂質メディエーターによるアレルギー炎症の制御2018

    • Author(s)
      平形 寿彬、李 賢哲、横溝 岳彦
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 69 Pages: 569-575

    • Related Report
      2018 Research-status Report
  • [Presentation] カルボキシルエステラーゼ2の消化器癌における発現調節機構の解明2020

    • Author(s)
      張 順、伊志嶺 百々子、小平 佳典、折田 創、小林 敏之、樋野 興夫、横溝 岳彦、福永 哲、李 賢哲
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] C型肝炎治療薬ソホスブビルのカルボキシルエステラーゼ阻害活性の検討2020

    • Author(s)
      李 賢哲、伊志嶺 百々子、横溝 岳彦
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪酸不飽和化酵素FADS2欠損マウスにおける脂質プロファイル異常2019

    • Author(s)
      李 賢哲、李 慶賢、平形 寿彬、横溝 岳彦
    • Organizer
      第61回 日本脂質生化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高度不飽和脂肪酸欠乏時における脂質関連遺伝子発現の変動2019

    • Author(s)
      李 慶賢、李 賢哲、横溝 岳彦
    • Organizer
      第61回 日本脂質生化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Regulatory mechanism of expression of polyunsaturated fatty acids-related genes2019

    • Author(s)
      李 慶賢、李 賢哲、横溝 岳彦
    • Organizer
      第60回 国際脂質生物科学会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-02-19  

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