| Project/Area Number |
15590756
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
SATOH Shinji Kyushu University, Kyushu University Hospital, Assistant Professor, 大学病院, 講師 (60274445)
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| Co-Investigator(Kenkyū-buntansha) |
SUMINOTO Hideki Kyushu University, Medical Institution of Bioregulation, Professor, 生体防衛医学研究所, 教授 (30179303)
INOUE Ryuji Kyushu University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究院, 助教授 (30232573)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Transient receptor potential channel / G protein / Ca^<2+> channel / Angiotensin II / Apoptosis / Calcineurin / Heart failure / Transient Receptor Potential Protein / GTP-binding Protein / 心筋細胞肥大 / Ca^<2+> / アデノウィルス・ベクター |
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| Research Abstract |
We performed 1)In vitro study using cultured cells and 2)In vivo study using a rat model with heart failure.
1)TRP7 transfection study using HEK293 cells and rat neonatal cultured cardiomyocytes.
(1)Ca^<2+>-transient activated by carbachol was augmented in TRP7-transfected HEK cells more than in non-transfected cells, suggesting that TRP7 acts as G protein-coupled Ca^<2+> channels.
(2)Apoptosis was induced in TRP7-transfected myocardial cells, and the incidence of apoptosis was further increased when activated by angiotensin II(Ang II), as detected by TUNEL stain. The Ang II-induced apoptosis was inhibited by Ang II receptor blocker, Ca^<2+> channel blocker, and calcineurin inhibitor.
(3)In apoptotic cells, the expression of atrial natriuretic factor(ANF) was decreased, and the destruction of actin fibers was noted.
(4)The expression of TRP7 mRNA was increased by Ang II, and this increase was inhibited by Ang II receptor blocker, Ca^<2+> channel blocker, and calcineurin inhibitor.
2)Role of TRP7 in Dahl salt-sensitive rats with heart, failure.
(1)The expression of TRP7 mRNA was increased in the myocardium of heart failure rats, and this increase was inhibited by long-term treatment with an angiotensin-converting enzyme inhibitor.
(2)Apoptosis was increased in the myocardium of heart failure rats, and this increase was inhibited by long-term treatment with an angiotensin-converting enzyme inhibitor.
Based on these results, TRP7 may act as receptor-activated Ca^<2+> channels mediating Ang II-induced myocardial apoptosis via calcineurin-dependent pathway, and this signaling may contribute to the process of apoptosis leading to heart failure.
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