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Elucidation of myocardial amino acid metabolic regulation by novel mitochondrial protein and the development to treat for heart failure

Research Project

Project/Area Number 15K09144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Matoba Satoaki  京都府立医科大学, 医学(系)研究科(研究院), 教授 (10305576)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords心不全 / ミトコンドリア / エネルギー代謝 / キラルアミノ酸 / Dアミノ酸 / Dグルタミン酸 / Dグルタミン酸サイクラーゼ / アミノ酸代謝 / Dアミノ酸 / アミノ酸 / D-アミノ酸 / D-グルタミン酸 / 9030617O03Rik / D-グルタミン酸シクラーゼ
Outline of Final Research Achievements

We investigated functions of the novel mammalian mitochondrial protein 9030617O03Rik and showed decreased expression under conditions of heart failure. Genomic sequence analyses showed partial homology with a bacterial aspartate/glutamate/hydantoin racemase. Subsequent determinations of all free amino acid concentrations in 9030617O03Rik-deficient mice showed high accumulations of D-glutamate in heart tissues. This is the first time that a significant amount of D-glutamate was detected in mammalian tissue. Further analysis of D-glutamate metabolism indicated that 9030617O03Rik is a D-glutamate cyclase that converts D-glutamate to 5-oxo-D-proline. Hence, this protein is the first identified enzyme responsible for mammalian D-glutamate metabolism, as confirmed in cloning analyses. These findings suggest that D-glutamate and 5-oxo-D-proline have bioactivities in mammals through the metabolism by D-glutamate cyclase.

Report

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

    (5 results)

All 2017 2016 Other

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

  • [Journal Article] D-Glutamate is metabolized in the heart mitochondria.2016

    • Author(s)
      M. Ariyoshi, M. Katane, K. Hamase, Y. Miyoshi, M. Nakane, A. Hoshino, Y. Okawa, Y. Mita, S. Kaimoto, M. Uchihashi, K. Fukai, K. Ono, S. Tateishi, D. Hato, R. Yamanaka, S. Honda, Y. Fushimura, E. Iwai-Kanai, N. Ishihara, M. Mita, H. Homma, and S. Matoba.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 43911-43911

    • DOI

      10.1038/srep43911

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Mitochondiral quality control in cardiac disease2017

    • Author(s)
      的場聖明
    • Organizer
      日本循環器学会 総会
    • Place of Presentation
      石川県 金沢市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Novel mitochondrial protein D-glutamate cyclase decreases during the progression of heart failure2017

    • Author(s)
      Tateishi S et al.
    • Organizer
      アメリカ心臓協会年次集会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 心筋エネルギー代謝研究グループ・主な業績

    • URL

      http://www.f.kpu-m.ac.jp/k/med2/group/kenkyu/k-01g.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 【論文掲載】心不全の解明に前進 新たな代謝酵素を発見

    • URL

      http://www.kpu-m.ac.jp/doc/news/2017/20170309_2.html

    • Related Report
      2016 Research-status Report

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

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