2004 Fiscal Year Final Research Report Summary
Role of DNA repair proteins in development of the tolerance after ischemic preconditioning
| Project/Area Number |
15591507
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Akita University |
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Principal Investigator |
SUZUKI Akira Akita University, School of Medicine, Assistant Professor, 医学部, 助手 (10311573)
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| Co-Investigator(Kenkyū-buntansha) |
KINOUCHI Hiroyuki Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (30241623)
SUGAWARA Taku Akita University, School of Medicine, Lecturer, 医学部, 講師 (80241660)
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| Project Period (FY) |
2003 – 2004
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| Keywords | cerebral ischemia / ischemic tolerance / hippocampal CA1 subregion / apoptosis / cytochrome c / caspases / APE |
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| Research Abstract |
Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1), is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the involvement of this protein in the development of neuronal tolerance to global cerebral ischemia after ischemic preconditioning. Adult male Sprague-Dawley rats were subjected to either 5 minutes of lethal global ischemia with or without 3 minutes of sublethal ischemic preconditioning or 3 minutes of ischemia only. Neuronal injury was histologically assessed, and DNA damage was visualized by in situ labeling of DNA fragmentation and DNA gel electrophoresis. APE expression was also examined by immunohistochemistry and Western blot analysis. Hippocampal CA1 neurons underwent DNA-fragmented cell death 3 days after 5 minutes of ischemia. However, these neurons showed a strong tolerance to 5 minutes of ischemia 1 to 3 days after ischemic preconditioning. Immunohistochemistry showed virtually no constitutive expression of APE proteins in CA1 neurons ; however, ischemic preconditioning induced neuronal APE expression 1 to 3 days later. Western blot confirmed an increase in Ku 70 in this region at the same time. The temporal and spatial expression of APE corresponded to tolerance of the hippocampal CA1 neurons to subsequent ischemia, suggesting the involvement of APE protein in the development of neuronal tolerance after ischemic preconditioning.
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Research Products
(10 results)
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[Journal Article] Mitochondrial cytochrome c-and Smac-dependent apoptosis in cerebral ischemia : role of oxidative signaling.2004
Author(s)
Sugawara T, Ferrand-Drake M, Yu F, Maier C, Hoyte EE, Chan PH
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Journal Title
Maturation phenomenon in cerebral ischemia V.((eds) Buchan AM, Ito U, Colbourne F, Kuroiwa T, Klatzo I)(Springer-Verlag, Berlin)
Pages: 53-62
Description
「研究成果報告書概要(欧文)」より
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