| Project/Area Number |
09307013
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Osaka University |
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Principal Investigator |
TADA Michihiko Osaka University Medical School, Professor, 医学部, 教授 (90093434)
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| Co-Investigator(Kenkyū-buntansha) |
OTSU Kinya Osaka University Medical School, Assistant Professor, 医学部, 助手 (20294051)
NISHIDA Masashi Osaka University Medical School, Assistant Professor, 医学部, 助手 (40283783)
KUZUYA Tsunehiko Osaka University Medical School, Associate Professor, 医学部, 助教授 (80150340)
星田 四朗 大阪大学, 医学部, 助手 (80238732)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥37,400,000 (Direct Cost: ¥37,400,000)
Fiscal Year 1998: ¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 1997: ¥22,800,000 (Direct Cost: ¥22,800,000)
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| Keywords | Ca signaling / sarcoplasmic reticulum / Ca release channel / phospholamban / heart failure / gene expression / Caジクナリング / カルシウムシグナリング / 興奮収縮連関 / 筋小胞体カルシウム遊離チャネル / 心筋症 / 遺伝子診断 |
|---|
| Research Abstract |
Muscle contractility is regulated by Intracellualr calcium. Upon depolarization of plasma membrane, Ca is released into cytoplasm from the sarcoplasmic reticulum through Ca release channel, leading to muscle contraction. On the other hand, Ca uptake by Ca ATPase in sarcoplasmic reticulum lowers Ca concentration to induce muscle relaxation. Ca, which binds to calsequestrin, is stored in the sarcoplasmic reticulum. The activity of Ca ATPase is regulated by phospholamban. The sarcoplasmic reticulum plays an important role in exitation-contraction coupling. The changes in expression levels of the Ca signaling proteins in cardiac hypertrophy and heart failure may influence on a cardiac performance. In this study, we analyzed the mechanism for gene expression of Ca release channel and phospholamban. We identified the promotor regions in the genes and possible transcriptional factors for expression. Our structure- function analysis of Ca ATPase and phopholamban revealed that a functional unit of phopholamban is a monomer and an oligomer serves as a pool of the molecule. We showed that extracellular disuffide bonds of connexin 43 are crucial for formation of gap junction, through which cardiomyocytes communicate each other.
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