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Research for stress signalling underlying neuro-degenerating disease

Research Project

Project/Area Number 22500341
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionToho University

Principal Investigator

KOBAYASHI Masaaki  東邦大学, 医学部, 講師 (70246693)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsヒポカルシン / ストレス応答 / 神経細胞死 / MLK3 / カルシウムシグナリング / mixed lineage kinase
Research Abstract

Acceleration of apoptosis and activation of caspases are observed in hippocalcin deficient hippocampal neurons. Here we examined the relation between hippocalcin and Hippocalcin and mixed lineage kinase (MLK)3, which is known to lead neuronal apoptosis.MLK3 were co-immunoprecipitated in a calcium-dependent manner. Immunocomplex kinase assay revealed that MLK3 kinase activity in hippocalcin deficient hippocampus was higher than that in wild type mice. In vitro kinase assay showed that recombinant hippocalcin inhibited MLK3 kinase activity in a calcium-dependent manner. Kainic acid-induced neuronal apoptosis was accelerated in hippocalcin deficient mice accompanied with enhancement in MLK3 activity. These results indicate that hippocalcin inhibits MLK3 kinase activity via direct interaction, and down-regulates apoptosis signaling in hippocampal neurons.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results) Presentation (15 results) Book (1 results)

  • [Journal Article] Hippocalcin mediates calcium-dependent translocation of brain-type creatine kinase (BB-CK) in hippocampal neurons2012

    • Author(s)
      Masaaki Kobayashi, Makoto Hamanoue, Tamotsu Masaki, Yoshitaka Furuta, Ken Takamatsu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 3-4 Issue: 3-4 Pages: 142-147

    • DOI

      10.1016/j.bbrc.2012.10.125

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hippocalcin. Encyclopedia of Signaling Molecules2012

    • Author(s)
      Kobayashi M, Takamatsu K
    • Journal Title

      (ed: Choi S) Springer Reference, USA

      Pages: 865-871

    • DOI

      10.1007/978-1-4419-0461-4_251

    • ISBN
      9781441904607, 9781441904614
    • Related Report
      2012 Final Research Report
  • [Journal Article] Role of hippocalcin in mediating Aβtoxicity2012

    • Author(s)
      Lim YA, Giese M, Shepherd C, Halliday G, Kobayashi M, Takamatsu K, Staufenbiel M, Eckert A, Gotz J
    • Journal Title

      Biochim Biophys Acta - Molecular Basis of Disease

      Volume: 1822 Issue: 8 Pages: 1247-1257

    • DOI

      10.1016/j.bbadis.2012.04.007

    • Related Report
      2012 Final Research Report
  • [Journal Article] Hippocalcin and KCNQ channels contribute to the kinetics of the slow afterhyperpolarization2012

    • Author(s)
      Kim KS, Kobayashi M, Takamatsu K, Tzingounis AV
    • Journal Title

      Biophysical Journal

      Volume: 103(12) Issue: 12 Pages: 2446-2454

    • DOI

      10.1016/j.bpj.2012.11.002

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hippocalcin

    • Author(s)
      Masaaki Kobayasi, et.al.
    • Journal Title

      Encyclopedia

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of hippocalcin in mediating Aβ toxicity

    • Author(s)
      Yun-An Lim, et.al.
    • Journal Title

      BBA-Molecular Basis of Disease

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hippocalcin

    • Author(s)
      Masaaki Kobayasi, et al.
    • Journal Title

      Encyclopedia

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Hippocalcin protects hippocampal neurons, against MLK3-mediated excitotoxin damage2013

    • Author(s)
      Kobayashi M, Takamatsu K
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-28
    • Related Report
      2012 Final Research Report
  • [Presentation] Binding profile and intracellular colocalization between hippocalcin and creatine kinase B subunit2012

    • Author(s)
      小林正明, 浜之上 誠, 高松 研
    • Organizer
      第55回日本神経化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2012-10-01
    • Related Report
      2012 Final Research Report
  • [Presentation] 脳虚血による神経細胞死の誘導機構および抑止機構の解析2011

    • Author(s)
      小林正明
    • Organizer
      第65回東邦医学会総会 平成22年度医学研究科推進研究報告
    • Place of Presentation
      東京
    • Year and Date
      2011-11-11
    • Related Report
      2012 Final Research Report
  • [Presentation] 脳虚血による神経細胞死の誘導機構および抑止機構の解析2011

    • Author(s)
      小林正明
    • Organizer
      第65回東邦医学会総会
    • Place of Presentation
      東邦大学医学部(東京都)
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒポカルシンを介する脳型クレアチンキナーゼ(BB-CK) のカルシウム依存性膜移行2011

    • Author(s)
      小林正明, 浜之上 誠, 高松 研
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-16
    • Related Report
      2012 Final Research Report
  • [Presentation] ストレス応答性神経細胞死の誘導機構および抑制機構の解析2011

    • Author(s)
      小林正明、細野なつえ
    • Organizer
      第137回東邦医学会例会
    • Place of Presentation
      東邦大学(東京都)
    • Year and Date
      2011-02-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 細野なつえ: ストレス応答性神経細胞死の誘導機構および抑制機構の解析2011

    • Author(s)
      小林正明
    • Organizer
      第137回東邦医学会例会
    • Place of Presentation
      東京
    • Year and Date
      2011-02-04
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒポカルシンと脳型クレアチンキナーゼ(CKB) の結合特性2011

    • Author(s)
      小林正明,浜之上 誠、高松 研
    • Organizer
      第88回日本生理学会大会・第116回日本解剖学会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] 脳型クレアチンキナーゼのカルシウム/ヒポカルシン依存性トランスロケーション2010

    • Author(s)
      小林正明, 浜之上 誠, 高松 研
    • Organizer
      Nuero2010(第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会)
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] 脳型クレアチンキナーゼのカルシウム/ヒポカルシン依存性トランスロケーション2010

    • Author(s)
      小林正明、浜之上誠、高松研
    • Organizer
      Neuro 2010
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Year and Date
      2010-09-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒポカルシンを介した脳型クレアチンキナーゼのカルシウム依存性トランスロケーション2010

    • Author(s)
      小林正明, 浜之上 誠, 高松 研
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      岩手
    • Year and Date
      2010-05-21
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒポカルシンを介した脳型クレアチンキナーゼのカルシウム依存性トランスロケーション2010

    • Author(s)
      小林正明、浜之上誠、高松研
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Year and Date
      2010-05-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Binding profile and intracellular colocalization between hippocalcin and creatine kinase B subunit.

    • Author(s)
      小林正明
    • Organizer
      第55回日本神経化学会大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 神経変性に関与するストレスシグナルの解析

    • Author(s)
      小林正明
    • Organizer
      第141回東邦医学会例会
    • Place of Presentation
      東邦大学医学部臨床講堂(東京)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hippocalcin protects hippocampal neurons, against MLK3-mediated excitotoxin damage.

    • Author(s)
      Kobayashi M
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      船堀タワーホール(東京都)
    • Related Report
      2012 Annual Research Report
  • [Book] Encyclopedia of Signaling Molecules.2012

    • Author(s)
      Kobayashi M,
    • Publisher
      Springer Reference, USA.
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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