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Is Mg ion a novel second messenger for regulating energy metabolism?

Research Project

Project/Area Number 16H01751
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Life / Health / Medical informatics
Research InstitutionKeio University

Principal Investigator

OKA KOTARO  慶應義塾大学, 理工学部(矢上), 教授 (10276412)

Co-Investigator(Kenkyū-buntansha) チッテリオ ダニエル  慶應義塾大学, 理工学部(矢上), 教授 (00458952)
舟橋 啓  慶應義塾大学, 理工学部(矢上), 准教授 (70324548)
Research Collaborator Arimura Yuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥39,520,000 (Direct Cost: ¥30,400,000、Indirect Cost: ¥9,120,000)
Fiscal Year 2018: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2017: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2016: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywords生体生命情報学 / シグナル伝達 / 神経科学 / 細胞・組織 / 神経化学
Outline of Final Research Achievements

We investigated the dynamics of intracellular magnesium (Mg) ions comprehensively and quantitatively by several fluorescent imagings, and clarified the novel role of Mg ion as an intracellular signal transducer. In the research on culture neurons in the early develpmental stages, we revealed that an inhibitory neurotransmitter, GABA, was involved in the maturation of neural circuits. This effect of GABA was mediated by the mobilization of intracellular Mg ions. In particular, downstream of Mg ion signal transduction, which has not been clarified so far, it suppressed the activity of the intracellular signal molecule ERK, promoted the activity of CREB, and promoted the activity of mTOR. Especially for the mTOR signal, it was shown that Mg ion plays a role of a switch to turn on / off the activity.

Academic Significance and Societal Importance of the Research Achievements

Mgイオンはその重要性については広く理解されていたものの、具体的な役割については未知の点が多かった。今回の研究では、Mgイオンの細胞内動員は同じ2価の陽イオンであるCaとは大きく異なることを明らかにするとともに、これまで不明であったMgイオン下流の情報伝達過程について明らかにすることに成功した。特に主要なシグナル経路であるERK、CREB、mTORのリン酸化過程をMg動員が異なる仕方で制御していることを明らかにした。これらの結果はMgイオンの生理的な役割の理解を深めるとともに、様々な細胞レベルでの疾患や病態を理解する一助になるものと期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] GABA-Induced Intracellular Mg2+ Mobilization Integrates and Coordinates Cellular Information Processing for the Maturation of Neural Networks2018

    • Author(s)
      Ryu Yamanaka, Yutaka Shindo, Kohji Hotta, Koji Suzuki, Kotaro Oka
    • Journal Title

      Current Biology

      Volume: 28 Issue: 24 Pages: 3984-3991

    • DOI

      10.1016/j.cub.2018.10.044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transitional correlation between inner-membrane potential and ATP levels of neuronal mitochondria2018

    • Author(s)
      Suzuki R、 Hotta K、Oka K
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1

    • DOI

      10.1038/s41598-018-21109-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Transient Rise in Free Mg 2+ Ions Released from ATP-Mg Hydrolysis Contributes to Mitotic Chromosome Condensation2018

    • Author(s)
      Maeshima Kazuhiro、Matsuda Tomoki、Shindo Yutaka、Imamura Hiromi、Tamura Sachiko、Imai Ryosuke、Kawakami Syoji、Nagashima Ryosuke、Soga Tomoyoshi、Noji Hiroyuki、Oka Kotaro、Nagai Takeharu
    • Journal Title

      Current Biology

      Volume: 28 Issue: 3 Pages: 444-451

    • DOI

      10.1016/j.cub.2017.12.035

    • NAID

      120006380520

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress2016

    • Author(s)
      Yamanaka R, Tabata S, Shindo Y, Hotta K, Suzuki K, Soga T, Oka K
    • Journal Title

      Scientific Reports

      Volume: 6-30027 Issue: 1 Pages: 30027-30027

    • DOI

      10.1038/srep30027

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] An Artificial Reaction Promoter Modulates Mitochondrial Functions via Chemically Promoting Protein Acetylation2016

    • Author(s)
      Yutaka Shindo; Hirokazu Komatsu; Kohji Hotta; Katsuhiko Ariga; Kotaro Oka
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 29224-29224

    • DOI

      10.1038/srep29224

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered expression of Mg2+ transport proteins during Parkinson's disease-like dopaminergic cell degeneration in PC12 cells.2016

    • Author(s)
      Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K
    • Journal Title

      Biochim Biophys Acta

      Volume: 1863(8) Issue: 8 Pages: 1979-1984

    • DOI

      10.1016/j.bbamcr.2016.05.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Mg2+ as a second messenger in early developmental stages of neurons.2019

    • Author(s)
      Oka K.
    • Organizer
      IV International Magnesium Symposium “MAGNESIUM IN HEALTH AND DISEASE”
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Characterization of neural cells derived from human dental pulp stem cells.2018

    • Author(s)
      Ariumura Y, Kikuchi T, Yamanaka R, Shido Y, Hotta K, Mochizuki M, Oka K.
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞内局所でのマグネシウムイオンのFRETイメージング2018

    • Author(s)
      新藤豊,山中龍,鈴木孝治,堀田耕司,岡浩太郎
    • Organizer
      第27回日本バイオイメージング学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞内マグネシウムイメージング2018

    • Author(s)
      新藤豊,山中龍,鈴木孝治,堀田耕司,岡浩太郎
    • Organizer
      第27回日本バイオイメージング学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト歯髄幹細胞から誘導した神経細胞とアストロサイトの特徴付け2018

    • Author(s)
      有村勇輝, 菊池憧子, 山中龍, 新藤豊, 望月真衣, 中原貴, 岡浩太郎
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Estimation of metabolic energy balance in neurons by using fluorescent imagings2017

    • Author(s)
      Iizumi M、 Suzuki R、 Yamanaka R、 Shindo Y、 Hotta K、 Oka K
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Native dynamics of mitochondrial membrane potential and ATP levels in growing neurites visualized by simultaneous imaging2017

    • Author(s)
      Suzuki R、 Hotta K、 Oka K
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characteristics of neuronal differentiated cells derived from human dental pulp stem cells (hDPSCs)2017

    • Author(s)
      Arimura Y、 Kikuchi T、 Yamanaka R、 Shindo Y、 Hotta K、 Mochizuki M、 Nakahara T、 Oka K
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mitochondria, energy metabolism and Mg ions -their correlation with neurodegeneration2017

    • Author(s)
      Oka K
    • Organizer
      2017 University of Cologne-Kaohsiung Medical University Joint Symposium on Cancer, Infection, Aging, Neurodegeneration
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生理的条件下の細胞形態変化に伴うATPレベル変動の定量的解析2017

    • Author(s)
      鈴木李夏、堀田耕司、岡浩太郎
    • Organizer
      日本生物物理学会第55回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 局在化プローブを用いた細胞内マグネシウムイオンのFRETイメージング2017

    • Author(s)
      新藤豊、山中龍、鈴木孝治、堀田耕司、岡浩太郎
    • Organizer
      第26回バイオイメージング学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Na+/Mg2+交換体阻害によるグルタミン酸興奮毒性の緩和2017

    • Author(s)
      新藤豊、山中龍、鈴木孝治、堀田耕司、岡浩太郎
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生理的条件下で伸長する神経突起におけるミトコンドリア動態の多面的解析2017

    • Author(s)
      鈴木李夏、堀田耕司、岡浩太郎
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト歯髄幹細胞から誘導した神経細胞とアストロサイトの特徴付け2017

    • Author(s)
      有村勇輝、菊池憧子、山中龍、新藤豊、堀田耕司、望月真衣、中原貴、岡浩太郎
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 蛍光イメージング法によるエネルギー代謝評価2017

    • Author(s)
      飯泉美弦、鈴木李夏、山中龍、新藤豊、堀田耕司、岡浩太郎
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリア輸送・膜電位・ATPと神経伸展の相関解析2016

    • Author(s)
      鈴木 李夏 , 堀田 耕司, 岡 浩太郎
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば国際会議場(茨城県・つくば市)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Simultaneous imaging of ATP levels and membrane potential in mitochondria during axonal transport2016

    • Author(s)
      Suzuki R, Hotta K, Oka K
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      San diego(USA)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 伸長する神経突起でのミトコンドリア輸送・膜電位・ATP同時イメージング2016

    • Author(s)
      鈴木 李夏,堀田 耕司,岡 浩太郎
    • Organizer
      第25回日本バイオイメージング学会学術集会
    • Place of Presentation
      名古屋市立大学(愛知県・名古屋市)
    • Year and Date
      2016-09-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analysis of mitochondrial movement and its ATP production in elongating neurons2016

    • Author(s)
      Suzuki R, Hotta K, Oka K
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Is Mg ion a new second messenger?2016

    • Author(s)
      Oka K
    • Organizer
      Symposium on Ultrasensitive Protein Detection and Magnesium Homeostasis
    • Place of Presentation
      高雄(台湾)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 生体の科学 Vol.68 No.5 cAMPやcGMPなどのセカンドメッセンジャーのイメージング2017

    • Author(s)
      岡浩太郎
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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