Estimation of coupling factor 6-induced vascular damage and utilization for drug discovery
| Project/Area Number |
21590946
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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 | Hirosaki University |
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Principal Investigator |
OSANAI Tomohiro 弘前大学, 大学院・医学研究科, 准教授 (00169278)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Ken 弘前大学, 大学院・医学研究科, 教授 (20185549)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Coupling factor 6 / Angiotensin II / Vascular smooth muscle cells / Mesenteric arteriole / Spontaneously hypertensive rat / Sponteneously hypertensive rat / Wister Kyoto rat / Arachidonic acid / Efrapeptin / Vascular smooth muscle cell / Microarray / ATP / Acidosis / Calcium / c-Src / Arteriole / Antibody |
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| Research Abstract |
Coupling factor 6 (CF6) bound to ss-sunbunit of ATP synthase at the surface of vascular smooth muscle cells (VSMC), and induced proton influx into the cytoplasm via degradation of ATP to ADP. CF6 induced influx of extracellular calcium and increased intracellular free calcium concentration in response to angiotensin II. These responsiveness of calcium to CF6 was enhanced in spontaneously hypertensive rats (SHR) compared with Wister Kyoto rats, and were abolished after pretreatment with anti-CF6-C terminus antibody, suggesting that the C-terminus of CF6 is involved in the action of its peptide. In the experiment of mesenteric arteries, CF6 in the arteriole induced the contraction in response to angiotensin II via activation of tyrosine kinase c-Src, and it was attenuated by pretreatment with anti-CF6-C terminus antibody. Overall, these suggest that inhibition of CF6 may antagonize the action of angiotensin II as other inhibitors of rennin-angiotensin system.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke : A possible linkage to homocysteine2010
Author(s)
Osanai T, Fujiwara N, Sasaki S, Metoki N, Saitoh G, Tomita H, Nishimura T, Shibitani S, Yokoyama H, Konta Y, Magota K, Okumura K
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Journal Title
Ann Med
Volume: 42
Pages: 79-86
Related Report
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[Journal Article] Overexpression of coupling factor 6 causes cardiac dysfunction under high salt diet in mice2010
Author(s)
Ashitate T, Osanai T, Tanaka M, Magota K, Echizen T, Izumiyama K, Yokoyama H, Shibutani S, Hanada K, Tomita H, Okumura K
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Journal Title
J Hypertens
Volume: 28
Pages: 2243-2251
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