| Project/Area Number |
10670656
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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 |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
KAWASHIMA Seinosuke Kobe University, Kobe University Hospital, Lecturer, 医学部・附属病院, 講師 (10177678)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Mitsuhiro Kobe University, School of Medicine, Professor, 医学部, 教授 (40135794)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | oxidative stress / antioxidant / heart failure / viral myocarditis / endothelin / cardiac hypertrophy / MAP kinase / 肥大 / p42 / p44MAPキナーゼ / 一酸化窒素 / 心筋炎 |
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| Research Abstract |
We investigated the role of oxidative stress on the pathogenesis of failing heart.
1)In coksacckievirus-induced viral myocarditis in mice, we examined the effects of purobucol (PB), an antioxidaive drug, on the process of myocardial damage. In PB-treated virus-infected mice, superoxide production and activity of inducible NO synthase in the heart were decreased compared with those in non-treated virus-infected mice. Reduction in these inflammatory mediators in PB-treated animals were associated with attenuated activation of the redox-sensitive transcriptional factor, NFκB, in the heart. Along with these improvements, the mortality after virus infection was reduced in PB-treated mice. On the other hand, we could not find the improvement of the process of myocardial damage by PB-treatment in failing heart after myocardial infarction. Therefore, the extent of participation of oxidative stress in the pathophysiology of failing heart may differ depending on the
2)The intracellular signal transduction in endothelin (ET)-induced cardiomyocyte hypertrophy was investigated. In cultured neonatal rat cardiomyocytes, endothelin induced increases in protein synthesis, fetal gene expression and sarcomere arrangement. In association with these changes, ET induced activations of both p42/p44MAP(ERK1/2) kinase and p38 MAP kinase. Inhibition of ERK1/2 activation by pharmacological inhibitors and the dominant negative mutant of MEK blocked hypertrophic response to ET. However inhibition of p38 MAP kinase is necessary for ET-induced cardiomyocyte hypertrophy.
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