Molecular mechanisms of cardiac hypertrophy/heart failure by Ca2+ transporter candidates and its application to drug discovery
Project/Area Number |
17K08610
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | Fukuoka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
田頭 秀章 福岡大学, 医学部, 講師 (90735028)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | イオン輸送体 / 心不全 / 心肥大 / 病態モデル動物 / 創薬 |
Outline of Final Research Achievements |
Solute carrier (SLC) transporters are membrane proteins that facilitate the transport of substrates across biological membranes. We confirmed that the targeted SLC transporter can transport Ca2+, using mammalian cell expression system. Interestingly, cardiac-specific transgenic mice of the target SLC transporter exhibited cardiac hypertrophy, reduced cardiac function, and early sudden death. Furthermore, we observed abnormal Ca2+ transients in cultured cardiac myocytes from the cardiac-specific transgenic mice. These results suggest that upregulation of the targeted SLC transporter may induce cardiac hypertrophy/heart failure. We established the screening system for the specific inhibitors, which might be useful therapeutically.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、SLCトランスポーター群の中から新規なCa2+輸送体(標的SLC輸送体分子)を見出した。この遺伝子改変マウスを用いた病態生理学的解析から、標的SLC輸送体分子は、心肥大・心不全の誘発因子である可能性が示唆された。本研究成果は、心肥大・心不全の病態解明に貢献するのみならず、新たな心不全治療薬の開発に繋がることが期待される。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Reduced expression of Na+ /Ca2+ exchangers is associated with cognitive deficits seen in Alzheimer's disease model mice2018
Author(s)
Moriguchi S, Kita S, Fukaya M, Osanai M, Inagaki R, Sasaki Y, Izumi H, Horie K, Takeda J, Saito T, Sakagami H, Saido TC, Iwamoto T, Fukunaga K
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Journal Title
Neuropharmacology
Volume: 131
Pages: 291-303
DOI
Related Report
Peer Reviewed
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[Journal Article] Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger.2018
Author(s)
Bai X, Ihara E, Hirano K, Tanaka Y, Nakano K, Kita S, Iwamoto T, Ogino H, Hirano M, Oda Y, Nakamura K, Ogawa Y.
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Journal Title
Cell Mol Gastroenterol Hepatol
Volume: 5
Issue: 3
Pages: 209-221
DOI
Related Report
Peer Reviewed
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[Journal Article] Reduced CaM Kinase II and CaM Kinase IV Activities Underlie Cognitive Deficits in NCKX2 Heterozygous Mice.2018
Author(s)
Moriguchi S, Kita S, Yabuki Y, Inagaki R, Izumi H, Sasaki Y, Tagashira H, Horie K, Takeda J, Iwamoto T, Fukunaga K.
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Journal Title
Mol Neurobiol.
Volume: 55(5)
Pages: 3889-3900
DOI
Related Report
Peer Reviewed
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