| Project/Area Number |
17591461
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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 |
Thoracic surgery
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| Research Institution | The University of Tokyo (2006)
National Research Institute for Child Health and Development (2005) |
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Principal Investigator |
TAKEUCHI Koh The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10302027)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Arata The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (70190874)
MAEDA Katsuhide The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (40313150)
DOI Yoshio The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10361958)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Ischemic injury / Re-oxygenation injury / glucose metabolism / fatty acid metabolism / ceramide / apoptosis / 心筋細胞 / 虚血-再酸素化 |
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| Research Abstract |
This study has been designed to see the intracellular event in myocytes during hypoxia-reoxygenation process. Cultured myocytes were prepared and exposed to hypoxia for 90 minutes followed by 60 minutes of re-oxygenation. Glucose extraction, lactate production, apoptotic cell death, extracellular regulated protein kinase (ERKs) phophorylation were mainly measured. Specific sphyngomyelinase inhibitor, D-609 was also tested to see if there was protective effects on myocytes exposed to hypoxia followed by re-oxygenation insult. During hypoxia lactate production was significantly higher in control than D-609 group, whereas glucose uptake was significantly reduced in control group compared to D609 group. Apoptotic cell death was clearly decreased with D 609 treatment with significantly reduced phosphorylation of ERKs. However one of the marker for cell necrosis, fatty acid binding protein FABP was not different between the group, suggesting that clearly detected apoptosis is different from necrotic cell death. Ceramide Protein synthesis measured by Western immunoblotting was significantly lower in D 699 group than control. This may imply that D609 is contributed to a reduction of ceramide accumulation in hypoxia-reoxygenation exposed myocytes. Based on our findings, we conclude that accumulation of ceramide might be associated with impairement of glucose metabolism, possibly fatty acid metabolism as well as significantly increased apoptotic cell death. Suppression of ceramide accumulation in myocytes might be contributed to reduced apoptotic cell death and extracellular regulated protein kinase phosphorylation as well as improved glucose metabolism.
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