| Project/Area Number |
17590227
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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 |
General pharmacology
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| Research Institution | Juntendo University |
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Principal Investigator |
MURAYAMA Takashi Juntendo University, Department of Pharmacology, Associate Professor (10230012)
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| Co-Investigator(Kenkyū-buntansha) |
KUREBAYASHI Nagomi Juuntendo University School of Medicine, Department of Pharmacology, Associate Professor (50133335)
OBA Toshiharu Nagoya City University, Graduate School of Medical Sciences, Departments of Cell Physiology, Associate professor (50008330)
中郡 昭人 順天堂大学, 医学部, 助手 (50236824)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | cardiac hypertrophy / heart failure / ryanodine receptor / calcium ion / sarcoplasmic reticulum / 細胞内カルシウム / カルモジュリン / 細胞内Ca2+ |
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| Research Abstract |
Type 2 ryanodine receptor (RyR2) is a Ca^<2+> release channel in the sarcoplasmic reticulum (SR) in the cardiac muscle and plays a pivotal role in regulation of intracellular Ca^<2+> concentration. RyR2 forms a multi-protein complex with several associated proteins which affect the activity of RyR2. In this study, we examined the abnormality in the RyR2 complex in cardiac hypertrophy (CH)/heart failure (HF) by using animal model. Ca^<2+> transients of the myocytes isolated from the Dahl rats, a model for CH/HF, were significantly smaller than those from the control rats. This was due to a reduced Ca^<2+> content in the SR. The channel activity of Dahl rat RyR2 was higher than the control RyR2 in ryanodine binding assay and single channel recordings. To address the underlying mechanisms of the increased activity, protein expression profiles of the isolated SR were determined by 2D electrophoresis. Many proteins were decreased or increased in the Dahl rat SR in compared with control rat SR. We are currently examining the function of several candidate proteins by RNA interference assay. Taken together, these findings suggest that alterations in the protein expression may cause the increased activity of RyR2 in the CH/HF, which leads to reduction in the stored Ca^<2+> and decreased Ca^<2+> transients.
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