| Project/Area Number |
09470162
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SEKO Yoshinori University of Tokyo, Hospital,, 医学部・附属病院, 助手 (30240708)
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| Co-Investigator(Kenkyū-buntansha) |
TOBE Kazuyuki University of Tokyo, Hospital,, 医学部・附属病院, 助手 (30251242)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1998: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1997: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | ischemia / reperfusion / hypoxia / reoxygenation / intracellular signal transduction / humoral factor / VEGF / autocrine / レドックス / 酸化ストレス / 細胞内シグナル伝達 |
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| Research Abstract |
1. Molecular mechanism of cardiac response to hypoxia/reoxygenation : We showed that hypoxia/reoxygenation activated Src family tyrosine kinases, p21^<ras>, three MAPK family member kinases and their upstream as well as downstream kinases, Jak/STAT tyrosine kinases, and a transcription factor ATF-2. The signal transduction cascades activated by these stimuli were at least partly different. 2. Autocrine mechanism via certain humoral factors involved in the activation of intracellular signaling induced by hypoxia/reoxygenation : (A)We showed that the activation of intracellular signaling in cardiac myocytes induced by hypoxia was mediated by VEGF in an autocrine fashion. This autocrine mechanism seemed to play a protective role in cardiac response to hypoxic stresses by suppressing apoptotic process and increasing adhesion between cardiac myocytes and extracellular matrix. (B)We found that similar autocrine mechanism was involved in the activation of intracellular signaling in cardiac my
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ocytes induced by reoxygenation, and we are now isolating and purifying the humoral factor. 3. Molecular mechanism of cardiac response to relative hypoxia : We showed that the activation of intracellular signaling in cardiac myocytes induced by pulsatile mechanical stretch (relative hypoxia) was also mediated by VEGF in an autocrine fashion. 4. Serum levels of the humoral factor, which mediates cardiac response to ischemia/reperfusion(hypoxia/reoxygenation) : (A)By meas uring the serum levels of VEGF in patients with acute myocardial infarction undergoing early reperfusion therapy, we demonstrated that VEGF could be a sensitive indicator of ischemic (hypoxic) state. This also strongly supported the data of 2. (A). (B)We are now isolating and purifying the humoral factor involved in the activation of intracellular signaling induced by reoxygenation, and we suppose that the serum levels of the humaral factor will be a good indicator of reperfused (reoxygenated) state in the heart of these patients. Less
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