Research on signal transduction of ischemic neuronal death

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 13470283
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Gunma 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)
• Project Period (FY): 2001 – 2003
• Keywords: cerebral ischemia / MAP kinase / signal transduction

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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