2007 Fiscal Year Final Research Report Summary
Molecular mechanisms underlying abnormal functions in RyR2 complex in cardiac hypertrophy/heart failure
| 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)
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| Project Period (FY) |
2005 – 2007
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| Keywords | cardiac hypertrophy / heart failure / ryanodine receptor / calcium ion / sarcoplasmic reticulum |
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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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[Presentation] Generation of the GFP-tagged type 1 ryanodine receptor mutants by transposon-based random insertion approach2008
Author(s)
Murayama, T, Kashiyama, T, Oyamada, H, Kobayashi, T, Kurebayashi, N, Sakurai, T
Organizer
Biophysical Society 52nd Annual Meeting
Place of Presentation
Long Beach, CA
Year and Date
20080202-06
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of a cytoplasmic loop between M7b and M8 transmembrane helices of RyR1 in Ca^<2+> channel gating2007
Author(s)
Murayama, T, Oyamada, H, Oba, T, Oguchi, K, Kurebayashi, N
Organizer
Biophysical Society 51st Annual Meeting
Place of Presentation
Baltimore, MD
Year and Date
20070303-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Postulated role of interdomain interactions within the type 1 ryanodine receptor in dysfunction of Ca^<2+> release channel in malignant hyperthermia2006
Author(s)
Murayama, T, Oyamada, H, Kurebayashi, N, Oba, T, Hara, H, Wakebe, K, Ikemoto, N, Ogawa, Y
Organizer
Biophysical Society 50th Annual Meeting
Place of Presentation
Salt Laky City, UT
Year and Date
20060218-22
Description
「研究成果報告書概要(欧文)」より
