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Qualitative and quantitative of low-and medium-molecular weight metabolites in exosomal fraction of serum and its application to schizophrenia-risk diagnosis

Research Project

Project/Area Number 19K07175
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionToho University

Principal Investigator

ONOZATO Mayu  東邦大学, 薬学部, 講師 (50610094)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血清 / エクソソーム / LC-MS/MS / 誘導体化 / チオール化合物 / アミノ酸 / ARMS / 統合失調症 / エクソソーム、 / ペプチド
Outline of Research at the Start

LC-MS/MS用の高感度化標識試薬 COXA-OSuを用いるオリジナルLC-MS/MS法によりエクソソームに含まれる低~中分子(ペプチド)を同定・定量する。この方法を活用し、ARMS患者が統合失調症などを発症するリスクを予測可能な診断補助ツールとしての有用性を検討する。
具体的には、① 本LC-MS/MS法を用いて、ヒト血清由来エクソソームに含有される特有の低~中分子(ペプチド)を見出し、新規ペプチドであれば、そのアミノ酸配列の解明、② 本学医療センターとの共同研究によりARMS及び健常対照群の血清由来エクソソーム低分子~中分子(ペプチド)濃度の比較・統計解析を行う。

Outline of Final Research Achievements

Decrease in the serum methionine/homocysteine ratio may be a risk factor for developing psychosis during the transition from at-risk mental state (ARMS) to first-episode psychosis (FEP), and may prove to be a useful marker of the phase between ARMS and FEP.
A composition of thiol-containing amino acids in exosomal fraction of human serum was similar to those in the corresponding native serum.
A novel derivatization reagent, CIMa-OSu, is able to determine trace D-amino acids, and furthermore, to distinguish peaks derived from primary amino acids from other amines easily.

Academic Significance and Societal Importance of the Research Achievements

ARMS群のエクソソームに関する報告はほとんどないため、本成果は新たな同疾患の診断法として医療や生命科学研究の発展に繋がる可能性がある。血清エクソソームの定量値の異常が分かれば、統合失調症の発症機構解明に繋がることも期待できる。新規アミノ酸標識化試薬の活用は、エクソソームに含まれるペプチド解析、特に新規ペプチドの同定にも有効であると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Development of derivatization reagents bearing chiral 4-imidazolidinone for distinguishing primary amines from other amino acids and application to the liquid chromatography-tandem mass spectrometric analysis of miso2021

    • Author(s)
      Tatsuya Sakamoto, Mayu Onozato, Shusuke Uekusa, Hideaki Ichiba, Maho Umino, Mika Shirao, Takeshi Fukushima
    • Journal Title

      Journal of Chromatography A

      Volume: 1652 Pages: 462341-462341

    • DOI

      10.1016/j.chroma.2021.462341

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LC-MS/MS analysis of thiol-containing amino acids in exosomal fraction of serum.2020

    • Author(s)
      Onozato M, Kobata K, Sakamoto T, Ichiba H, Fukushima T
    • Journal Title

      J Chromatogr Sci.

      Volume: 58 Issue: 7 Pages: 636-640

    • DOI

      10.1093/chromsci/bmaa028

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alterations in methionine to homocysteine ratio in individuals with first-episode psychosis and those with at-risk mental state.2020

    • Author(s)
      Onozato M, Uta A, Magarida A, Fukuoka N, Ichiba H, Tsujino N, Funatogawa T, Tagata H, Nemoto T, Mizuno M, Fukushima T
    • Journal Title

      Clin Biochem.

      Volume: 77 Pages: 48-53

    • DOI

      10.1016/j.clinbiochem.2019.12.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] タンデム型質量分析計により1級アミン構造を識別する4-イミダゾリジノン型試薬の創製と味噌成分アミノ酸分析への応用2021

    • Author(s)
      坂本 達弥、小野里 磨優、植草 秀介、一場 秀章、海野 真帆、白尾 美佳、福島 健
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 初回エピソード精神病及び精神病発症危険状態におけるHcy-Met代謝の変動2020

    • Author(s)
      小野里 磨優、雅樂 晏里沙、曲田 彩夏、福岡 尚実、一場 秀章、辻野 尚久、田形 弘実、舩渡川 智之、根本 隆洋、水野 雅文、福島 健
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 東邦大学薬学部薬品分析学教室

    • URL

      https://www.lab.toho-u.ac.jp/phar/Analchem/index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] 東邦大学薬学部薬品分析学教室

    • URL

      https://www.lab.toho-u.ac.jp/phar/Analchem/article/index.html

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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