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Research on signal transduction of ischemic neuronal death

Research Project

Project/Area Number 13470283
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionGunma University

Principal Investigator

SAITO Nobuhito  Gunma University, Department of Neurosurgery, Professor, 医学部, 教授 (60262002)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Akio  Gunma University, Department of Neurosurgery, Assistant Professor, 医学部, 講師 (60261856)
TOSAKA Masahiko  Gunma University, Department of Neurosurgery, staff, 医学部, 助手 (40323357)
豊田 富勝  東京大学, 医学部, 助手 (00251257)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordscerebral ischemia / MAP kinase / signal transduction / 免疫抑制剤
Research Abstract

MEK is in the course of MAP kinase cascade and bears the signal transduction of growth factors and protects cells from various insults. However, it is reported recently that inhibition of MEK activity may protect neurons from excitotoxic insults. In this study, we aimed to clarify weather MEK mediates death signal or not.
Constitutively active MEK1 was adenoviral transdused in primary cultured neurons. Four days after MEK1 adenovirus infection, neuronal death was evaluated by LDH measurement of the supernatant. MEK1 induced neuronal death dose-dependently. A MEK inhibitor, U0126, prevented the death. Thus, MEK1 was considered to mediate death signal in the cultured neurons.
To examine the effect of MEK inhibitor in vivo, focal cerebral ischemia by middle cerebral artery occlusion was induced in rats after administration of U0126 or vehicles. In our experiment, U0126 did not have protective effect against cerebral ischemia. Further investigation is indicated to clarify the difference.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Horiguchi K, Tomizawa Y, Tosaka M, Ishiuchi S, Kurihara H, Mori M, Saito N: "Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21.3 in brain tumors."Oncogene. 30. 7862-7865 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asai A, Tanahashi N, Qiu JH, Saito N, et al.: "Selective Proteasomal Dysfunction in the Hippocampal CA1 Region After Transient Forebrain Ischemia"J Cereb Blood Flow Metab. 22・6. 705-710 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugawara Ki K, Kurihara H, Negishi M, Saito N, et al.: "Nestin as a marker for proliferative endothelium in gliomas"Lab Invest. 82・3. 345-351 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mochizuki T, Asai A, Saito N, et al.: "Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide"J.Biol.Chem. 277. 2790-2797 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T Tosaka M, Hashiba Y, Saito N, et al.: "Contractile responses to reactive oxygen species in the canine basilar artery in vitro : selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger."Acta Neurochir. 144. 1305-1310 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horiguchi K, Tomizawa Y, Tosaka M, Ishiuchi S, Kurihara H, Mori M, Saito N: "Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21.3 in brain tumors."Oneogene. 30. 7862-7865 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asai A, Tanahashi N, Qiu JH, Saito N, et al.: "Selective Proteasomal Dysfunction in the Hippocampal CA1 Region After Transient Forebrain Ischemia"J.Cereb.Blood Flow Metab.. 22. 705-710 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sugawara K, Kurihara H, Negishi M, Saito N, Nakazato Y, Sasaki T, Takeuchi T.: "Nestin as a Marker for Proliferative Endothelium in Gliomas"Lab.Invest.. 82. 345-351 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mochizuki T, Asai A, Saito N, Tanaka S, Katagiri H, Asano T, Nakane M, Tamura A, Kuchino Y, Kitanaka C, Kirino T.: "Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide."J.Biol.Chem.. 277. 2790-2797 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tosaka M, Hashiba Y, Saito N, Imai H, Shimizu T, Sasaki T.: "Contractile responses to reactive oxygen species in the canine basilar artery in vitro : selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger."Acta Neurochir.. 144. 1305-1310 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horiguchi K, Tomizawa Y, Tosaka M, Ishiuchi S, Kurihara H, Mori M, Saito N: "Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21.3 in brain tumors."Oncogene. 30. 7862-7865 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Asai A, Tanahashi N, Qiu JH, Saito N, et al.: "Selective Proteasomal Dysfunction in the Hippocampal CA1 Region After Transient Forebrain Ischemia"J Cereb Blood Flow Metab. 22・6. 705-710 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugawara Ki K, Kurihara H, Negishi M, Saito N, et al.: "Nestin as a marker for proliferative endothelium in gliomas"Lab Invest. 82・3. 345-351 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tosaka M., Okajima F., Hashiba Y., Saito N., et al.: "Sphingosine 1-phosphate contracts canine basilar arteries in vitro and in vivo : possible role in pathogenesis of cerebral vasospasm"Stroke. 32. 2913-2919 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noda Y., Okada Y., Saito N., Setou M., Xu Y., et al.: "KIFC3, a microtubule minus end-directed motor for the apical transport of annexin XIIIb-associated Triton-insoluble membranes"J Cell Biol. 155. 2913-2919 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mochizuki T., Asai A., Saito N., et al.: "Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide"J. Biol. Chem. 277. 2790-2797 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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