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An analgesic neuropeptide endomorphin may be produced by RNA editing induced by oxidative stress

Research Project

Project/Area Number 26670288
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pain science
Research InstitutionKyushu University

Principal Investigator

Matsushima Ayami  九州大学, 理学(系)研究科(研究院), 准教授 (60404050)

Co-Investigator(Kenkyū-buntansha) KOYANAGI KANAKO  北海道大学, 情報科学研究科, 准教授 (20362840)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords遺伝子 / ゲノム / 生体分子 / 脳・神経 / 生理活性 / ペプチド / 疼痛 / 鎮痛
Outline of Final Research Achievements

Endomorphin-1 and -2 are neuropeptides consisting of only 4 amino acid residues. Various biological functions of these peptides are known, for instance analgesic activity that is stronger than that of morphine and a relation with itching. However, to date a precursor protein of these peptides has never been uncovered. Many scientists today consider that the limited information from short peptide sequence makes it difficult to find peptide genes by in silico genomic searches. In the present study, we intended to perform RNA-seq determinations combined with an in silico genomic search for the peptide precursor protein. We succeeded in finding an endomorphin-like peptide, although this was not exactly the same as endomorphins. The synthetic peptide corresponding to the endomorphin-like amino acid sequence has a weak binding affinity for opioid receptors.

Report

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

    (25 results)

All 2016 2015 2014 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) Remarks (3 results)

  • [Journal Article] Specific affinity-labeling of the nociceptin ORL1 receptor using a thiol-activated Cys(Npys)-containing peptide ligand.2016

    • Author(s)
      A. Matsushima, H. Nishimura, Y. Matsuyama, X. Liu, T. Costa, and Y. Shimohigashi
    • Journal Title

      Biopolymers: Peptide Science

      Volume: なし Issue: 4 Pages: 460-469

    • DOI

      10.1002/bip.22792

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ORL1 Nociceptin Receptor Response of Opioid Peptides Derived from Proenkephalin Precursor Protein.2016

    • Author(s)
      Motomatsu, Y., Nishimura, H., Matsusyama, Y., Liu, X., Matsushima, A., and Shimohigashi. Y.
    • Journal Title

      Peptide Science 2015

      Volume: - Pages: 181-182

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GPCR functional role of Phe-269 and Phe-221 in the molecular switching of ORL1 nociceptin receptor activation.2015

    • Author(s)
      Takesue, Y., Nishimura, H., Liu, X., Matsushima, A., and Shimohigashi. Y.
    • Journal Title

      Peptide Science 2014

      Volume: - Pages: 203-204

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Receptor selectivity and specificity of a series of opioid peptides latent in the proenkephalin precursor protein.2015

    • Author(s)
      Motomatsu, Y., Nishimura, H., Matsumoto, Y., Kuramitsu, Y., Inamine, S., Matsushima, A., and Shimohigashi. Y.
    • Journal Title

      Peptide Science 2014

      Volume: - Pages: 205-206

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An in silico genomic search of endomorphin-like opioid peptides.2015

    • Author(s)
      atsu, Y., and Shimohigashi. Y.
    • Journal Title

      Peptide Science 2014

      Volume: - Pages: 281-282

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The molecular switching of ORL1 nociceptin receptor in activation/inactivation.2015

    • Author(s)
      Nishimura, H., Li, J., Isozaki, K., Takesue, Y., Liu, X., Shimohigashi, M., Inamine, S., Matsushima, A., and Shimohigashi. Y.
    • Journal Title

      Peptide Science 2014

      Volume: - Pages: 201-202

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An in silico genomic search of endomorphin-like opioid peptides2015

    • Author(s)
      Matsushima, A., Koyanagi, O.K., Nishimura, H., Inamine, S., Motomatsu, Y., and Shimohigashi. Y.
    • Journal Title

      Peptide Science 2014

      Volume: - Pages: 201-202

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] N-Methylthioacetylation of RYYRIK-NH2 with enhanced specific binding affinity and high antagonist activity for nociceptin ORL1 receptor2014

    • Author(s)
      J. Li, H. Nishimura, A. Matsushima, and Y. Shimohigashi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 22 Issue: 21 Pages: 5721-5726

    • DOI

      10.1016/j.bmc.2014.09.049

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tritium-Labelled Isovaleryl-RYYRIK-NH2 as Potential Antagonist Probe for ORL1 Nociceptin Receptor2014

    • Author(s)
      S. Inamine, H. Nishimura, J. Li, K. Isozaki, A. Matsushima, T. Costa, and Y. Shimohigashi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 22 Issue: 21 Pages: 5902-5909

    • DOI

      10.1016/j.bmc.2014.09.018

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple and Simultaneous Cys→Ala Mutations of ORL1 Nociceptin Receptor to Identify the Affinity Binding site of Cys(Npys)-Elongated RYYRIK Peptide Antagonist2014

    • Author(s)
      Matsushima, A., Nishimura, H., Inamine, S., and Shimohigashi, Y.
    • Journal Title

      Peptide Science 2013

      Volume: - Pages: 413-4144

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structure-activity Studies on the Halogenated Phe-containing Neuropeptide Substance P Analogs2014

    • Author(s)
      Kuramitsu, Y., Nishimura, H., Nakamura, R., Suyama, K., Matsushima, A., Nose, T., and Shimohigashi, Y.
    • Journal Title

      Peptide Science 2013

      Volume: - Pages: 319-320

    • Related Report
      2014 Research-status Report
  • [Journal Article] Specific Role of Phe Residues in Opioid Peptide Met-enkephalin- Arg-Phe in Binding to All Three Opioid Receptors2014

    • Author(s)
      Motomatsu, Y., Nishimura, H., Matsumoto, Y., Inamine, S., Kuramitsu, Y., Matsushima, A., and Shimohigashi, Y.
    • Journal Title

      Peptide Science 2013

      Volume: - Pages: 317-318

    • Related Report
      2014 Research-status Report
  • [Presentation] プロエンケファリン前駆体からプロセッシングされる全オピオイドペプチドの受容体サブタイプ特異性2015

    • Author(s)
      元松 雄大・西村 裕一・松本 結香・蔵満 由美・稲嶺 翔吾・劉 暁輝・松島 綾美・下東 康幸
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ORL1疼痛受容体活性化における新規な分子スイッチ2015

    • Author(s)
      武末祐貴、西村裕一、劉 暁輝、松島綾美、下東康幸
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ORL1 nociceptin receptor response of opioid peptides derived from proenkephalin precursor protein2015

    • Author(s)
      Yudai Motomatsu, Hirokazu Nishimura, Yutaka Matsuyama, Xiaohui Liu, Ayami Matsushima, and Yasuyuki Shimohigashi
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      平塚市中央公民館(平塚市)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Functional Role of the Phe-Phe Stacking Microswich in the ORL1 nociceptin receptor activation2015

    • Author(s)
      uuki Takesue, Hirokazu Nishimura, Xiaohui Liu, Ayami Matsushima, and Yasuyuki Shimohigashi
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      平塚市中央公民館(平塚市)
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 痛み増強受容体ORL1のPhe269は受容体活性化における新規な分子スイッチ2015

    • Author(s)
      武末祐貴、西村裕一、劉 暁輝、松島綾美、下東康幸
    • Organizer
      平成27年度日本生化学会九州支部例会
    • Place of Presentation
      九州大学箱崎キャンパス(福岡市)
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] プロエンケファリン前駆体タンパク質から産生されるオピオイドペプチドのオピオイド受容体サブタイプ選択性と活性化能2015

    • Author(s)
      元松雄大、西村裕一、松本結香、蔵満由美、稲嶺翔吾、劉 暁輝、松島綾美、下東康幸
    • Organizer
      リスクサイエンス研究フォーラム2014
    • Place of Presentation
      福岡大学セミナーハウス、福岡市
    • Year and Date
      2015-03-09
    • Related Report
      2014 Research-status Report
  • [Presentation] An in silico genomic serch of endomorphin-like opioid peptides2014

    • Author(s)
      松島綾美、小柳香奈子、西村裕一、稲嶺翔吾、元松雄大、下東康幸
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島大学蔵本キャンパス大塚講堂、徳島市
    • Year and Date
      2014-10-22 – 2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] GPCR functional role of Phe-269 and Phe-221 in the molecular switching of ORL1 nociceptin receptor activation2014

    • Author(s)
      武末祐貴、西村裕一、劉暁輝、松島綾美、下東康幸
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島大学蔵本キャンパス大塚講堂、徳島市
    • Year and Date
      2014-10-22 – 2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] ORL1・ノシセプチン受容体活性化における221位および269位Pheの構造要因2014

    • Author(s)
      武末祐貴、西村裕一、劉 暁輝、松島綾美、下東康幸
    • Organizer
      第51回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場、北九州市
    • Year and Date
      2014-06-28
    • Related Report
      2014 Research-status Report
  • [Presentation] Met-enkephalin-Arg-Pheの4位および7位Phe-フェニル基の異なるオピオイド受容体相互作用性2014

    • Author(s)
      元松雄大、西村裕一、松本結香、稲嶺翔吾、蔵満由美、松島綾美、下東康幸
    • Organizer
      第51回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場、北九州市
    • Year and Date
      2014-06-28
    • Related Report
      2014 Research-status Report
  • [Remarks] 構造機能生化学(研究室ホームページ)

    • URL

      http://lsfb.scc.kyushu-u.ac.jp

    • Related Report
      2015 Annual Research Report
  • [Remarks] 九州大学大学院理学研究院化学部門大学院理学府化学専攻構造機能生化学研究室

    • URL

      http://lsfb.scc.kyushu-u.ac.jp

    • Related Report
      2014 Research-status Report
  • [Remarks] 九州大学大学院理学研究院リスクサイエンス研究教育拠点

    • URL

      http://rsrc.scc.kyushu-u.ac.jp/index.html

    • Related Report
      2014 Research-status Report

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

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