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Functional elucidation of anti-inflammatory effect of omega-3 PUFAs focusing on the omega-3 PUFA specific metabolic pathway

Research Project

Project/Area Number 26860034
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

ISOBE Yosuke  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 基礎科学特別研究員 (80724335)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオメガ3脂肪酸 / 抗炎症作用 / シトクロムP450 / ω3脂肪酸 / 線維芽細胞 / リピドミクス
Outline of Final Research Achievements

Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) are well known to have anti-inflammatory effects. Previous studies have suggested that oxidation of double bond in the omega-3 position of EPA might be important for omega-3 PUFAs' anti-inflammatory actions. Here, we tried to identify enzyme(s) which is involved in the oxidation reaction of EPA, and to identify target molecule(s) of EPA-derived bioactive metabolites.
For enzyme identification, we have developed an assay system which can comprehensively evaluate oxidation activity of PUFA-metabolizing enzymes using transient gene expression in mammalian cells. By using this system, we identified several cytochrome P450s (CYPs) as candidates which oxidize double bond in the omega-3 position of EPA. In addition, we found that several G-protein coupled receptors (GPCRs) were activated by treatment of EPA-derived bioactive metabolites.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Total synthesis of four stereoisomers of (4Z,7Z,10Z,12E,16Z,18E)-14,20-dihydroxy-4,7,10,12,16,18-docosahexaenoic acid and their anti-inflammatory activities.2015

    • Author(s)
      Goto T, Urabe D, Masuda K, Isobe Y, Arita M, Inoue M.
    • Journal Title

      J Org Chem

      Volume: 80 Issue: 15 Pages: 7713-7726

    • DOI

      10.1021/acs.joc.5b01461

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Total synthesis of four stereoisomers of (5Z,8Z,10E,14Z)-12-hydroxy-17,18-epoxy-5,8,10,14-eicosatetraenoic acid and their anti-Inflammatory activities2015

    • Author(s)
      Goto, T.; Urabe, D.; Isobe, Y.; Arita, M.; Inoue, M.
    • Journal Title

      Tetrahedron

      Volume: 71 Issue: 43 Pages: 8320-8332

    • DOI

      10.1016/j.tet.2015.08.047

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 18-HEPE, an n-3 fatty acid metabolite released by macrophages, prevents pressure overload-induced maladaptive cardiac remodeling2014

    • Author(s)
      Endo J, Sano M, Isobe Y, Fukuda K, Kang JX, Arai H, Arita M.
    • Journal Title

      J. Exp. Med.

      Volume: 211 Issue: 8 Pages: 1673

    • DOI

      10.1084/jem.20132011

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of 14,22014

    • Author(s)
      Yoshiyuki Yokokura, Yosuke Isobe, Shinnosuke Matsueda, Ryo Iwamoto, Tomomi Goto, Takeshi Yoshioka, Daisuke Urabe, Masayuki Inoue, Hiroyuki Arai and Makoto Arita
    • Journal Title

      the journal of biochemistry

      Volume: 156 Issue: 6 Pages: 315

    • DOI

      10.1093/jb/mvu044

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] オメガ3脂肪酸の抗炎症作用についての包括的メタボローム解析2015

    • Author(s)
      磯部 洋輔、有田 誠
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(兵庫県・神戸市)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Identification of novel omega-3 EPA-derived anti-inflammatory mediators using a targeted lipidomics approach2015

    • Author(s)
      Yosuke Isobe, Tadafumi Kubota, Hiroyuki Arai, Daisuke Urabe, Masayuki Inoue, Makoto Arita
    • Organizer
      PLM2015
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2015-02-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of novel EPA-derived anti-inflammatory metabolites using a targeted lipidomics approach2014

    • Author(s)
      Yosuke Isobe, Makoto Arita
    • Organizer
      5th European Workshop on Lipid Mediator
    • Place of Presentation
      イスタンブール(トルコ)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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