Development of methods to evaluate myocardial phosphoinositide turnover using positron emitter labeled compounds
| Project/Area Number |
07670747
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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 First Department of Internal Medicine, Tohoku University, Assistant professor, 医学部・附属病院, 助手 (90250779)
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| Co-Investigator(Kenkyū-buntansha) |
IDO Tatsuo Cyclotron & Radiosotope Center, Tohoku University, Professor, サイクロトロン・RIセンター, 教授 (80134063)
ISHIDE Nobumasa First Department of Internal Medicine, Tohoku University, Associate professor, 医学部, 助教授 (40124549)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Positron emitter / Phosphoinositide turnover / Positron emission tomography / Diacylglycerol / Heart failure / Cardiac hypertrophy / ポジトロン断層装置 / プロテインキザ-ゼC |
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| Research Abstract |
We hypothesized that protein kinase C (PKC) is activated in left ventricular remodeling after myocardial infarction in rats. We measured the regional myocardial membranous PKC using in vitro autoradiography with [H-3] phorbol 12,13-dibutyrate (PDBu) in rats. Imaging plates and a computer-assisted image processing system were used (Ref. 1). The heart was removed 1,3,7,21 days, and 10 months after left coronary artery ligation. We found that [H-3] PDBu binding was increased in the infarcted region compared with the non-infarcted region 7 days after operation and remained higher than the non-infarcted region until 21 days after. Histological examination revealed that abundant fibroblast-like cells were present at the sites with the increased [H-3] PDBu binding. Furthermone, we investigated whether [C-11] diacylglycerol or [F-18] diacylglycerols could trace the myocardial phosphoinositide turnover (PI turnover), which closely relates to PKC activation, in rats 30 minutes after the injectio
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n. The radioactivity incorporated into the intermediates of PI turnover was predominant in the myocardium of rats injected with [C-11] diacylglycerol. In rats injected with [F-18] diacylglycerols, the intermediates of PI turnover were not the main metabolites. Finally, we also performed in vivo autoradiography in rats injected with [C-11] diacylglycerol 7 days after coronary artery ligation. The autoradiographic intensity at the infarcted regions tended to increase compared with that in the non-infarcted region. These results suggest that PI turnover and PKC was activated at the infarcted region, and that fibroblast-like cell may be responsible for these increased activity. We have shown that myocardial metabolic abnormality in patients with cardiomyopathy using positron emission tomography (Ref. 2). Our results also suggest that positron emitter labeled compounds and positron emission tomography have a potential role in visualizing the abnormalities of regional signal transduction as well as metabolic abnormalities in various heart disease patients. Less
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Report
(3 results)
Research Products
(8 results)
