2003 Fiscal Year Final Research Report Summary
DISORDER OF CARNITINE METABOLISM AND LIPD SIGNAL TRANSDUCTION IN MYOCARDIUM
| Project/Area Number |
14570655
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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 | NAGOYA UNIVERSITY |
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Principal Investigator |
OKUMURA Kenji NAGOYA UNIVERSITY, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (40262901)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Hajime NAGOYA UNIVERSITY, University Hospital, Medical Staff, 医学部附属病院, 医員
OGAWA Yasuhiro NAGOYA UNIVERSITY, University Hospital, Medical Staff, 医学部附属病院, 医員
MATSUI Hideo NAGOYA UNIVERSITY, University Hospital, Research Associate, 医学部附属病院, 助手 (00324434)
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| Project Period (FY) |
2002 – 2003
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| Keywords | cardiac hypertrophy / carnitine deficiency / diacylglycerol / fatty acid composition / ceramide / lipid signal transduction |
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| Research Abstract |
The visceral steatosis (JVS) mouse, a genetic model of systemic carnitine deficiency resulting from carnitine transport mutation, develops cardiac hypertrophy. We determined two putative lipid messengers, 1,2-diacylglycerol (DAG) and ceramide, in JVS and carnitine palmitoyltransferase-I (CPT-I) inhibitor etomoxir-treated mice because these lipids function as co-messengers in the myocardium via modification of protein kinase C activity. JVS mice were evaluated at 4 and 8 weeks of age. The effect of long-term etomoxir treatment on mice was investigated in control mice from 4 to 8 weeks of age. As a model of inhibited cardiac hypertrophy, carnitine-treated JVS (CT) mice were produced. Myocardial DAG and ceramide levels, and their fatty acid composition were measured. The heart/body weight ratio increased by 100% in JVS mice compared with that in controls, while that of CT mice was normalized in comparison with controls at 8 weeks of age. DAG markedly increased in both JVS and etomoxir-treated mice compared with that in controls, whereas it was decreased significantly in CT mice compared with that in JVS mice. Furthermore, the fatty acid composition of DAG was similar between JVS and moxir-treated mice ; in particular, 18:1 and 18:2 were significantly elevated in the myocardium. On the other hand, that of DAG in CT mice was similar to that of the control group. In contrast, no difference was observed in myocardial ceramide levels among the groups. Pharmacological intervention of etomoxir mimics changes in the lipid second messenger characteristic of genetic JVS mice. The results suggest that the increases in distinct DAG species might be involved in the pathogenesis of cardiac hypertrophy as a result of disorder of fatty acid transport.
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Research Products
(4 results)
