2000 Fiscal Year Final Research Report Summary
Diacylglycerol Kinases in Ventricular Remodeling
| Project/Area Number |
11670657
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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, Hospital, Assistant Prof., 医学部・附属病院, 助手 (90250779)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Kaoru Yamagata University, Dept. of Medicine, Professor, 医学部, 教授 (30234975)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Diacylglycerol / Diacylglycerol kinase / Ventricular remodeling / Captopril / Myocardial infarction / プロテインキナーゼC |
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| Research Abstract |
Diacylglycerol kinases (DGKs) attenuate the activity of PKC.Five DGK isozymes, α, β, γ, ε and ζ have been cloned and are revealed to be expressed in their unique patterns in the rat brain, whereas little is known about the expression and roles in hearts. We investigated whether DGK isozymes are expressed in rat hearts and localized and quantified the expression of these isozymes at different time points after myocardial infarction (MI). Northern blot analysis and in situ hybridization histochemistry revealed that α, ε and ζ isozymes are expressed in normal rat hearts, while α isozyme expression was very low. We then detailed the spatiotemporal distribution of mRNA for DGK isozymes at 3, 7 and 21 days after MI using in situ hybridization. Enhanced ζ isozyme expression was detected around the necrotic myocytes and at the border zone, with little expression in the necrotic area 3 and 7 days after MI.The ζ isozyme expression was detected in the center of the granulation tissue in the infarct area 21 days after MI.Immunohistochemistry revealed that granulocytes and macrophages were responsible for the increased ζ isozyme expression. In contrast, the expression of ε isozyme was predominant in the viable left ventricle throughout the experiment. Quantitative support by competitive RT-PCR was obtained for these findings. The expression of ε isozyme mRNA is downregulated by 29% in the viable myocardium of untreated MI rats compared with sham-operated rats. This was completely normalized by the treatment with captopril for 21 days after MI, which was associated with a 13% reduction in the heart /body weight ratio. We demonstrated, for the first time, that three DGK isozymes are expressed in the heart and that each isozyme may play different functional roles in LV remodeling after MI.
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[Publications] Namiuchi S, Kagaya Y, Chida M, Yamane Y, Takahashi C, Fukuchi M, Tezuka F, Watanabe J, Ido T, Shirato K.: "Regional and temporal profiles of phorbol 12, 13 - dibutyrate binding after myocardial infarction in rats : Effects of captopril treatment."J Cardiovasc Pharmacol. 35. 353-360 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Otani H, Kagaya Y, Yamane Y, Chida M, Ito K, Namiuchi S, Shiba N, Koseki Y, Ninomiya M, Ikeda J, Saito H, Maruoka M, Fujiwara T, Ido T, Ishide N, Shirato K.: "Long-term right ventricular volume overload increases myocardial FDG uptake in the interventricular septum in patients with atrial septal defect."Circulation. 101. 1686-1692 (2000)
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[Publications] Takahashi C, Kagaya Y, Namiuchi S, Takeda M, Fukuchi M, Otani H, Ninomiya M, Yamane Y, Kohzuki M, Watanabe J, Shirato K.: "Non selective ET receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival."J Cardiovasc Pharmacol. (in press.). (2001)
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