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Target identification and mechanism of action of neoechinulin A

Research Project

Project/Area Number 15K01808
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomolecular chemistry
Research InstitutionAzabu University

Principal Investigator

KAMISUKI Shinji  麻布大学, 獣医学部, 講師 (30553846)

Co-Investigator(Renkei-kenkyūsha) SUGAWARA Fumio  東京理科大学, 理工学部, 教授 (30192123)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords天然物 / 生理活性物質 / 神経保護効果 / 活性窒素 / 神経細胞死 / ファージディスプレイ / 標的タンパク質 / ケミカルバイオロジー
Outline of Final Research Achievements

Neoechinulin A is an indole alkaloid that protects neuronal PC12 cells from cytotoxicity induced by the peroxynitrite generator SIN-1, but the target proteins and precise mechanism of action of neoechinulin A were unclear. In this study, we employed a phage display screen to identify proteins that bind directly with neoechinulin A. Our findings identified two proteins, chromogranin B and glutaredoxin 3, as candidate target binding partners for the compound. QCM analyses revealed that neoechinulin A displays high affinity for both chromogranin B and glutaredoxin 3. RNA interference-mediated depletion of chromogranin B decreased the sensitivity of PC12 cells against SIN-1. Our results suggested chromogranin B is a plausible target of neoechinulin A.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2018 2017 2016 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Identification of proteins that bind to the neuroprotective agent neoechinulin A2018

    • Author(s)
      Kamisuki Shinji、Himeno Natsumi、Tsurukawa Yukine、Kusayanagi Tomoe、Takeno Masahiro、Kamakura Takashi、Kuramochi Kouji、Sugawara Fumio
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 3 Pages: 442-448

    • DOI

      10.1080/09168451.2018.1433018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neoechinulin A induced memory improvements and antidepressant-like effects in mice2016

    • Author(s)
      Sachie Sasaki-Hamada, Maho Hoshi, Yuki Niwa, Yudai Ueda, Aya Kokaji, Shinji Kamisuki, Kouji Kuramochi, Fumio Sugawara, Jun-Ichiro Oka
    • Journal Title

      Progress in Neuro-Psychopharmacology & Biological Psychiatry

      Volume: 71 Pages: 155-161

    • DOI

      10.1016/j.pnpbp.2016.08.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 神経保護物質ネオエキヌリンAの結合タンパク質の同定2018

    • Author(s)
      紙透伸治、姫野なつみ、鶴川幸音、草柳友恵、竹野正洋、鎌倉高志、倉持幸司、菅原二三男
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 真菌由来の新規生理活性物質の探索2017

    • Author(s)
      紙透伸治
    • Organizer
      第28回新薬創製談話会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 麻布大学基礎教育研究室・化学ホームページ

    • URL

      https://lab-navi.azabu-u.ac.jp/v-01-chemi/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Remarks] 麻布大学基礎教育研究室・化学ホームページ

    • URL

      http://www.azabu-u.ac.jp/lab/v/v_basic-chemi.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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