| Project/Area Number |
14370496
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo Medical University, Department of Anesthesiology |
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Principal Investigator |
ISHII Nagao Tokyo Medical University, Faculty of Medicine, Professor, 医学部, 教授 (00074865)
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| Co-Investigator(Kenkyū-buntansha) |
UCHINO Hiroyuki Tokyo Medical University, Faculty of Medicine, Assissstant Professor, 医学部, 講師 (60266476)
SHIBASAKI Futoshi Tokyo Metropolitan Institute of Medical Science Department of Molecular Physiology, Director, 東京都臨床医学総合研究所・細胞生理, 研究員
KUBO Yoshihisa Tokyo University of Pharmacy and Life Science, Faculty of Life Scienece, Professor, 生命科学部, 教授 (20080179)
高橋 俊明 東京医科大学, 医学部, 助手 (30349451)
近江 明文 東京医科大学, 医学部, 講師 (70246221)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | Hypoxia / Calcineurin / Mitochondrial Permeability Transition(MPT) / Cyclosporin A / FK506 / Cyclophilin D / Hypoxia Inducible Factor(HIF) / Na^+ / Ca^<2+>exchanger / Ca2_+濃度 / 免疫抑制剤 / DNA chip / NCX / カルシニューリン / イムノフィリン / 神経細胞死 / Calcineurin / 低酸素反応性因子(HIF) / Rat |
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| Research Abstract |
Hypoxic brain ischemia leads to severe damage as a similar form of delayed neuronal cell death in fore brain ischemia. We have been investigated the mechanisms of hypoxic ischemic brain damage in terms of the mechanisms of immunosuppressant, such as cyclosporin A(CsA) and FK506. From our results, Calcineurin and immunophilin signal transduction cascade play an important roles for neuroprotection. From our results, Calcineurin also regulates Ca^<2+> homeostasis, HIF(hypoxic inducible factor) and NCX(Na^+/Ca^<2+> exchanger). Calcineurin Especially, mitochondrial isomerase cyclophillinD paly a pivotal role to regulate the MPT(Mitochondrial Permeability Transition)pore formation, one of the prolyl cis/trans isomerase family members.
We also need further analysis to explore more mechanisms.
These results shed light on the clinical application and development of new drugs for the treatment of hypoxic ischemic damage in the brain as well as in the heart and liver.
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