| Project/Area Number |
06670715
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
HANDA Nobuo Osaka University, Medicine, Assistant, 医学部, 助手 (80228676)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Satoshi Osaka University, Hospital, Fellow, 医学部附属病院, 医員
KITAGAWA Kazuo Osaka University, Hospital, Fellow, 医学部附属病院, 医員
MATSUMOTO Masayasu Osaka University, Medicine, Assistant, 医学部, 助手 (20192346)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | tyrosine phosphorylation / cerebral ischemia / kainic acid / pp60c-src / radicicol |
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| Research Abstract |
Glutamate triggers neuronal degeneration following ischemia/reperfusion in the brain. However, the details of intracellular signal transduction that propagate cell death remain unknown. The present work investigated whether protein tyrosine phophorylation mediates neuronal death in the ischemic brain. Transient forebrain ischemia for 5-10 min in Mobgolian gerbils or intoxication of glutamate analogue (kainic acid, 12 mg/kg) in Sprague-dawley rats caused neuronal death selectively in the hippocampus 2-4 days or 1 day later, respectively. Under these conditions, 160,115,105,92,85 kDa proteins showed a significant increase in tyrosyl residue phosphorylation selectively in the hippocampus 3-12 h after ischemia or 4-8 h after kainic acid-induced seizures. Tyrosine kinase, including pp60c-src, were activated without a change of tyrosine phophatases. Administration of radicicol, a selective inhibitor of tyrosine kinases, attenuated stimulation of tyrosine phophorylation and hippocampal degeneration after ischemia or kainic acid injection. the results suggest that protein tyrosine phosphorylation might propagate delayd neuronal death in the amture hippocampus through glutamate overload after ischemia/reperfusion.
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