| Project/Area Number |
18500322
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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 |
Neurophysiology and muscle physiology
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| Research Institution | National Institute for Physiological Sciences |
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Principal Investigator |
URAMOTO Hiromi National Institute for Physiological Sciences, Cell Physiology, Fellow (50390696)
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| Co-Investigator(Kenkyū-buntansha) |
NUMATA Tomohiro National Institute for Physiological Sciences, Cell Physiology, Research Associate (20455223)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | ischemia-reperfusion / CFTR / heart / necrosis |
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| Research Abstract |
The final goal of our study is to elucidate the molecular mechanisms of the cardio-protective action involve CFTR against ischemia-reperfusion injury and then to contribute to knowledge about the molecular events leading to the ischemia-reperfusion injury and its protection. In the present study, our aim is to clarify that CFTR plays a protective role in ischemia-reperfusion injury, and how CFTR exerts the protective action using experimental ischemia-reperfusion systems both in vivo and in vitro. We have demonstrated that CFTR is able to reduce the infarct size in a manner distinct from a preconditioning effect in the in viva ischemia-reperfusion system. Activation of CFTR markedly minimized the infarct size even by administration of CFTR activators upon the onset of reperfusion, whereas administration of CFTR inhibitors aggravated the infarct size. In vivo experiments using adult CFTR knock-out mice conclusively demonstrated that the protective action of CFTR activators given at an onset of reperfusion requires expression of CFTR. In addition, we did attempt to elucidate the mechanism using an improved in vitro ischemia-reperfusion system which enables to promptly apply low partial pressure of oxygen and to administrate chemical agents upon early reperfusion. Observations of PI stainability and caspase 3/7 activity indicated that CFTR may be involved in the suppression of non-apoptotic cell death associated with the cardiac damage induced by ischemia-reperfusion. Microscopic observations of plasmamembrane staining also indicated that CFTR may play a suppressive role in the formation of blebs. Taken together, it is likely that the CFTR activity exerts a protective action against the ischemia-reperfusion injury by suppressing induction of necrotic cell death. However, it is necessary to make further experiments to firmly confirm the present conclusion because some of these in vitro results are still preliminary.
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