Role of signal transduction mediated by diacylglycerol and phosphatidic acid in cardiac hypertrophy
| Project/Area Number |
17590699
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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 | Tohoku University |
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Principal Investigator |
KAGAYA Yutaka Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (90250779)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Kaoru Yamagata University, School of Medicine, Professor, 医学部, 教授 (30234975)
KARIBE Akihiko Tohoku University, Hospital, Research Associate, 病院・助手 (80359504)
武田 守彦 東北大学, 病院・医員 (30375084)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Signal transduction / Cardiac hypertrophy / Cardiac failure / Diacylglycerol / Phsphatidic acid / ジアシルグリセロールキナーゼ / プロテインキナーゼC |
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| Research Abstract |
Protein kinase C that is activated by 1, 2-diacylglycerol (DG) plays an important role in the development of cardiac hypertrophy. Amount of DG in myocardium is regulated by DG kinase (DGK) as well as by phosphatidic acid phosphatase. We for the first time reported that DGK ε and DGK ζ are predominant isozymes that express in normal rat myocardium and that both isozymes play distinct roles in the process of ventricular remodeling after myocardial infarction.
At 28 days after operations, expression levels of DGK ε mRNA but not DGK ζ in left-ventricular myocardium significantly decreased in aortic-banded rats as compared with sham-operated rats. DGK ζ protein in the myocardium translocated from the particulate to the cytosolic compartment in aortic-banded rats. Furthermore, myocardial content of DG and PKCδ protein expression in the particulate fraction of the myocardium significantly increased in aortic-banded rats compared with sham-operated rats. These results suggest that DGK ε and DGK ζ play distinct roles in the development of pressure overload-induced cardiac hypertrophy and that the two isozymes are differentially regulated.
In transgenic mice with cardiac-specific overexpression of DGK ζ, extent of cardiac hypertrophy induced by aortic constriction did not differ from that in wild-type mice. This was also the case with pressure overload induced by continuous angiotensin II infusion. These findings are not consistent with those in the rat model of pressure overload-induced cardiac hypertrophy. On possible reason for the inconsistent results may be relatively low expression levels of the transgene of DGK ζ, in our transgenic model. A further study is required to solve this issue.
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Report
(3 results)
Research Products
(17 results)
