| Project/Area Number |
12470107
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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 |
Legal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIDA Ken-ichi University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40166947)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Masahiko University of Tokyo, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (70302669)
IWASE Hirotaro University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30272420)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥12,900,000 (Direct Cost: ¥12,900,000)
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| Keywords | myocardial infarction / ischemia / reactive oxygen species / lipid peroxidation / CO poisoning / cell death / intracellular signaling / 細胞内情報伝達系 / 活性酵素 / 一酸化炭素中毒 / チトクロームC / ラジカル / ヘム / リポキシナーゼ / ミトコンドリア / シクロプロパン |
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| Research Abstract |
1) Research on lipid per-oxidation and injury associated with carbon monoxide (CO) poisoning
There were both necrotic and apoptotic death in the basal ganglia, cortex, and hippocampus in a subacute CO poisoning case. The distribution of the lesions could not be explained by ischemia. In a rat model of rat CO poisoning (90 min CO exposure followed by 2 days recovery), there was necrosis, particularly in the sub-cortex. There was intense staining of a lipid peroxide product, 4-hydoroxynonenal (HNE), in the nuclei of the necrotic area. Hypothermia attenuated the necrosis and HNE-generation. Additionally, by the new assay system, another lipid per-oxidation product 7-hydroxysterol was shown to be increased after CO-exposure Hypothermia attenuated the 7-hydroxysterol generation induced by CO, indicating the involvement of lipid per-oxidation in the pathogenesis of CO poisoning and the possibility of clinical application of hypothermia.
2) Research on lipid peroxidation and injury associated with myocardial infarction
In a rat model of myocardial infarction, HNE and TNF-α was greatly increased, while the increase was attenuated by ischemic preconditioning (IP : cycles of brief time of ischemia-reperfusion) that mimic the pre-infarction angina. IP attenuated the enhanced TNF-α generation in the infracted myocardium and the activation of reactive oxygen-associated transcription factor NF κ B, which is known to promote nitric oxide-mediated cell injury and leukocyte-associated inflammation.
3) Research on the beneficial effect of CO exposure on ischemic cell death of cardio-myogenic H9c2 cells.
CO exposure attenuated the necrotic death, reactive oxygen generation and HNE formation in the H9c2 cells induced by chemical ischemia through MAP kinase/ERK pathway.
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