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Molecular basis of cerebrovascular disease with protein tyrosine phosphorylation in brain capillaries and therapeutic strategies

Research Project

Project/Area Number 20590091
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

TAKAGI Norio  Tokyo University of Pharmacy and Life Science, 薬学, 教授 (50318193)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脳虚血 / 脳血管 / チロシンリン酸化 / 血液脳関門 / 活性酸素種 / チロシンキナーゼ / タイトジャンクション / Occludin
Research Abstract

This study sought to determine the role of tyrosine phosphorylation of proteins in the pathophysiological alteration of the blood-brain barrier and subsequent brain injuries after stroke. This study demonstrates that the increase in the tyrosine phosphorylation of tight junctional protein occludin is linked to the disruption of tight junctions and the development of cerebral infarction after stroke and that the prostanoid EP1 receptor is involved in the tyrosine phosphorylation of occludin. In addition, this study suggests that protein tyrosine phosphorylation may be linked to the increase in the level of NADPH oxidase subunits, which are known as an important source of a reactive oxygen species, after stroke.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (14 results)

All 2011 2010 2009 2008

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (6 results)

  • [Journal Article] NADPH oxidase-mediated oxidative damage to proteins in the postsynaptic density after transient cerebral ischemia and reperfusion.2011

    • Author(s)
      Murotomi K, Takagi N, Takeo S, Tanonaka K
    • Journal Title

      Mol.Cell.Neurosci. 46(3)(corresponding author)

      Pages: 681-688

    • Related Report
      2010 Final Research Report
  • [Journal Article] NADPH oxidase-mediated oxidative damage to proteins in the postsynaptic density after transient cerebral ischemia and reperfusion2011

    • Author(s)
      Murotomi K, Takagi N, Takeo S, Tanonaka K?
    • Journal Title

      Mol.Cell.Neurosci.

      Volume: 46 Pages: 681-688

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mGluR1 antagonist decreased NADPH oxidase activity and superoxide production after transient focal cerebral ischemia.2010

    • Author(s)
      Murotomi K, Takagi N, Mizutani R, Honda T, Ono M, Takeo S, Tanonaka K
    • Journal Title

      J.Neurochem. 114(corresponding author)

      Pages: 1711-1719

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prostanoid EP1 receptor antagonist reduces blood-brain barrier leakage after cerebral ischemia.2010

    • Author(s)
      Fukumoto K, Takagi N, Yamamoto R, Moriyama Y, Takeo S, Tanonaka K
    • Journal Title

      Eur.J.Pharmacol. 640(1-3)(corresponding author)

      Pages: 82-86

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prostanoid EP1 receptor antagonist reduces blood-brain barrier leakage after cerebral ischemia.2010

    • Author(s)
      Fukumoto K, Takagi N, Yamamoto R, Moriyama Y, Takeo S, Tanonaka K
    • Journal Title

      Eur.J.Pharmacol.

      Volume: 640 Pages: 82-86

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of src activity decreases tyrosine phosphorylation of occludin in brain capillaries and attenuates increase in permeability of the blood-brain barrier after transient focal cerebral ischemia.2009

    • Author(s)
      Takenaga Y, Takagi N, Murotomi K, Tanonaka K, Takeo S
    • Journal Title

      J.Cereb.Blood Flow Metab. 29(6)(corresponding author)

      Pages: 1099-1108

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of src activity decreases tyrosine phosphorylation of occludin in brain capillaries and attenuates increase in permeability of the blood-brain barrier after transient focal cerebral ischemia.2009

    • Author(s)
      Takenaga Y, Takagi N, Murotomi K, Tanonaka K, Takeo S
    • Journal Title

      Journal of Cerebral Blood Flow and Metabolism 29

      Pages: 1099-1108

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mGluRl antagonist decreases tyrosine phosphorylation of NMDA receptor and attenuates infarct size after transient focal cerebral ischemia.2008

    • Author(s)
      Murotomi K, Takagi N, Takayanagi G, Ono M, Takeo S, Tanonaka
    • Journal Title

      Journal of Neurochemistry 105

      Pages: 1625-1634

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] NADPH oxidaseは一過性局所脳虚血後のシナプス後肥厚部関連タンパク質の酸化障害に寄与する2011

    • Author(s)
      室冨和俊、高木教夫、田野中浩一
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-22
    • Related Report
      2010 Final Research Report
  • [Presentation] NADPH oxidaseは一過性局所脳虚血後のシナプス後肥厚部関連タンパク質の酸化障害に寄与する2011

    • Author(s)
      室冨和俊、高木教夫、田野中浩一
    • Organizer
      第84回 日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 一過性局所脳虚血後のNADPH oixdaseを介したスーパーオキシド産生におけるmGluR1の関与2010

    • Author(s)
      室冨和俊,高木教夫,大野恵美,水谷玲子,竹尾聰,田野中浩一
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-16
    • Related Report
      2010 Final Research Report
  • [Presentation] 一過性局所脳虚血後のoccludinチロシンリン酸化と血液脳関門破綻へのSrcの関与2009

    • Author(s)
      室冨和俊,高木教夫,竹永悠司,竹尾聰,田野中浩一
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] Inhibition of protein tyrosine kinase prevents disruption of blood brain barrier and attenuates infarct size after transient focal cerebral ischemia2008

    • Author(s)
      K.Murotomi, N.Takagi, Y.Takenaga, S.Takeo, K.Tanonaka
    • Organizer
      第51回日本神経化学大会
    • Place of Presentation
      富山
    • Year and Date
      2008-09-11
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] 虚血性脳障害の病態解析と治療戦略2008

    • Author(s)
      高木教夫
    • Organizer
      第52回日本薬学会関東支部大会
    • Place of Presentation
      千葉
    • Year and Date
      2008-01-04
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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