Molecular mechanism of ischemic preconditioning
| Project/Area Number |
14570635
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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 | Yamagata University |
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Principal Investigator |
TAKEISHI Yasuchika Yamagata University, School of Medicine, Division of Cardiology, Pulmonology, and Nephrology, Associate Professor of Medicine, 医学部, 助教授 (40272067)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | signal transduction / BMK1 / ischemic preconditioning / MAP kinase / protein kinase C / hypertrophy / fatty acid metabolism / toll-like receptor / metabolism / Signal transuduction / Metabolism / Ischemic Preconditioning / Hypertrophy / Protein Kinase C |
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| Research Abstract |
Transgenic mice with cardiac specific overexpression of MEK5 were generated using α-myosin heavy chain promoter. MEK5 regulates BMK1 activity, and successful expression of transgene in the heart was confirmed by Nothern blotting. The mouse heart was excited, and coronary arteries were perfused retrogradely with Krebs buffer by the Langendorf method. Left ventricular pressure and its derivatives (dP/dt) were continuously monitored after global ischemia. In transgenic mouse hearts overexpressing MEK5, recovery of left ventricular pressure and dP/dt after ischemia was more prompt than in wild type mouse hearts. These data suggest that MEK5-BMK1 pathway may act as cardio-protective against myocardial ischemia, and be involved in molecular mechanisms of ischemic preconditioning.
Protein kinase C (PKC) is a key signaling molecule for both ischemic preconditioning and cardiac hypertrophy. Diacylglycerol kinase (DGK) is an enzyme responsible for controlling cellular levels of diacylglycerol, and possibly may work as an endogenous regulator of PKC activity. Hypoxia did not change levels of DGK gene expression in neonatal cardiomyocytes. Endothelin-1 increased DGK expression in cardiomyocytes. AP1 is a transcription factor downstream of PKC. AP1 DNA-binding activity was measured by luciferase reporter gene assay. AP-1 DNA binding activity was increased by endothelin-1. After transfection of DGK, endothelin-1 failed to increase API DNA-binding activity in a gene-dose dependent manner. These data suggest that DGK regulates PKC activity possible via controlling cellular diacylglycerol levels. DGK may work as an endogenous regulator of Gaq-coupled receptor signaling and modulate ischemic preconditioning and cardiac hypertrophy.
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Report
(4 results)
Research Products
(64 results)
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[Journal Article] Chronic hypertriglyceridemia in young Watanabe heritable hyperlipidemic rabbits accelerates endothelial and medial smooth muscle dysfunction.2004
Author(s)
Shishido T, Tasaki K, Takeishi_Y, Takasaki S, Miyamoto T, Itoh M, Takahashi H, Kubota I, Ito T, Katano Y, Wakabayashi I, Tomoike H
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Journal Title
Life Sci 74
Pages: 1487-1501
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Dynamic ^<123>I-BMIPP single photon emission computed tomography in patients with congestive heart failure : effect of angiotensin II type-1 receptor blockade.2004
Author(s)
Takeishi Y, Minamihaba O, Yamauchi S, Arimoto T, Hirono O, Takahashi H, Akiyama H, Miyamoto T, Nitobe J, Nozaki N, Tachibana H, Okuyama M, Fukui A, Kubota I
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Journal Title
Clin Cardiol 27
Pages: 204-210
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dynamic ^<123>I-MIBG SPECT reflects sympathetic nervous integrity and predicts clinical outcome in patients with chronic heart failure.2004
Author(s)
Arimoto T, Takeishi Y, Fukui A, Tachibana H, Nozaki N, Hirono O, Yamaguchi H, Itoh M, Miyamoto T, Tsunoda Y, Takahashi H, Kubota I, Okada A, Takahashi K
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Journal Title
Ann Nucl Med 18
Pages: 145-150
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.2003
Author(s)
Yamauchi S, Takeishi Y, Minamihaba O, Arimoto T, Hirono O, Takahashi H, Miyamoto T, Nitobe J, Nozaki N, Tachibana H, Okuyama M, Fukui A, Kubota I
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Journal Title
Nucl Med Commun 24
Pages: 901-906
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction.2003
Author(s)
Shishido T, Nozaki N, Yamaguchi S, Nitobe J, Miyamoto T, Takahashi H, Arimoto T, Maeda K, Yamakawa M, Takeuchi O, Akira S, Takeishi Y, Kubota I
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Journal Title
Circulation 108
Pages: 2905-2910
NAID
Description
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[Journal Article] Pulsed Doppler tissue imaging for the assessment of myocardial viability : comparison with ^<99m>Tc-MIBI perfusion imaging.2002
Author(s)
Minamihaba O, Takeishi Y, Hirono O, Yamauchi S, Fukui A, Okuyama M, Nozaki N, Akiyama H, Fatema K, Miyamoto T, Shishido T, Takahashi H, Fujiwara S, Takahashi K, Okada A, Kubota I
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Journal Title
Nucl Med Commun 23
Pages: 1197-1204
Description
「研究成果報告書概要(欧文)」より
Related Report
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