| Project/Area Number |
11470512
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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 |
応用薬理学・医療系薬学
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUDA Toshio Osaka Unive., Grad.Sch.of Pharmaceut.Sci., Professor, 薬学研究科, 教授 (00107103)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Hitoshi Osaka Univ., Grad.Sch.of Pharmaceut.Sci., Associate professor, 薬学研究科, 助教授 (30240849)
BABA Akemichi Osaka Univ., Grad.Sch.of Pharmaceut.Sci., Professor, 薬学研究科, 教授 (70107100)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | apoptosis / Ca^<2+> / MAP Kinase / cyclic GMP / astrocyte / microglia / neuron / neuroprotection / 過酸化水素 / ホスホジエステラーゼ / イブジラスト / ミトコンドリア / NF-κB / conditioned medium / β-アミロイド蛋白 / NF-KB / カルシニューリン |
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| Research Abstract |
The present study was carried out to clarify the mechanisms of cell death in cultured astrocytes, microglia and neurons. Incubation of cultured astrocytes in Ca^<2+>-containing medium after exposure to Ca^<2+>-free medium causes an increase in intracellular Ca^<2+> concentration followed by,delayed cell death. This injury is considered to be an in vitro model of ischaemia/reperfusion injury. This review summarizes our current studies on the mechanisms underlying the Ca^<2+>-mediated injury of cultured astrocytes and, target molecules, for drugs to prevent the reperfusion injury. Ca^<2+> reperfusion injury of astrocytes appears to be mediated by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species, calcineurin, caspase-3, and NF-κB are involved in the Ca^<2+> reperfusion injury. Several neuroprotective drugs including NGF, T-588, idebenone, and ibudilast prevent astrocyte apoptosis in the reperfusion injury models using Ca^<2+> depletion or hydrogen peroxide. The protective effects of these drugs are, mediated by phosphatidylinositol-3 kinase, mitogen-activated protein/extracellular signal-regulated kinase, nerve growth factor production, and cyclic GMP-dependent protein kinase. The analysis on the mechanism for the cyclic GMP effect indicates that the mitochondrial permeability transition pore plays a key role in, apoptotic events of cultured astrocytes
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