2001 Fiscal Year Final Research Report Summary
The effect of Neuregulin on cardiac myoctes - The relationship with isolated left ventricular noncompaction, and left ventricular remodeling
| Project/Area Number |
12670787
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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 |
Pediatrics
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| Research Institution | NIPPON MEDICAL SCHOOL |
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Principal Investigator |
FUKAZAWA Ryuji Nippon Medical School, Assistant, 医学部, 助手 (80277566)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Shunichi Nippon Medical School, Associate Professor, 医学部, 助教授 (50194436)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Neuregulin / Erb / Cardiac Myocytes / Cardiotoxicity |
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| Research Abstract |
The purpose of this study was to investigate how Neuregulin effected on cardiac myocytes. First, we confirmed Neuregulin anti-apoptotic effect, which was induced by Daunorubicin, on cardiomyocytes. The anti-apoptotic effect of Neuregulin was proved to be through the activation of Phospho Inositol-3 Kinase (PI3-K). Next, we compared Neuregulin signal transduction system on cardiomyocytes with Epidermal Growth Factor (EGF), which was the same peptide family with Neuregulin. We found Neuregulin activated both of MAP kinase (ERK) and PI3-K via ErbB-2 and ErbB-4 receptors. On the other hand, EGF only activated ERK via ErbB-1 and ErbB-2. We concluded ErbB-2 receptor greatly contribute to EGF family signal transduction. For more detail examination, we truncated ErbB-2 kinase domain and constructed dominant negative ErbB-2 adenovirus vector. We infected it into cardiomyocyte. Because of abundant expression of intrinsic ErbB-2, dominant negative ErbB-2 only reduced ErbB-2 phosphorylation by 20-30 %, and there were no changes about ERK and PI3-K activation. We tried next ErbB-2 anti-sense oligo method. However, ErbB-2 anti-sense oligo was lethal to cardiomyocytes, which probed ErbB-2 was indispensable for cardiomyocytes. We are now planning to use cardiomyocytes, which was induced by cord blood using 5' azathitizine, and tratuzamab (Herceptin) as ErbB-2 signal inhibitor for more detail study.
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Research Products
(1 results)
