Establishment of regulatory system against coupling factor 6-induced vascular damage
Project/Area Number |
24591089
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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 |
Circulatory organs internal medicine
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Research Institution | Hirosaki University |
Principal Investigator |
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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) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
Keywords | coupling factor 6 / IF1 / ATP synthase / acidosis / HEK293 / HUVEC / intracellular acidosis / ATPase IF1 / mitochondria / prostacyclin / diabetes / hypertension / cardiac hypertrophy |
Outline of Final Research Achievements |
Coupling factor 6 (CF6) converts the rotation of ecto-F1Fo complex, plasma membrane bound ATP synthase, from a clockwise mode of proton export (ATP synthesis) to a counter-clockwise mode of proton import (ATP hydrolysis), thereby leading to intracellular acidosis. Inhibitory peptide 1 (IF1) is a unidirectional inhibitor of ATP hydrolysis only, suggesting its possible antagonizing effect on CF6 without affecting ATP synthesis. In both human mature and immature IF1-transfected HEK 293 cells, IF1 protein was overexpressed in the cytosol fraction, and also was detected in the exosome fraction. ATP concentration in the culture media was decreased by CF6, but IF1 protein abolished its effect. The percentage of apoptotic cells was increased by CF6, but it was blocked by the transfection with mature or immature IF1. Overall, these suggest that IF1 may function as an endogenous inhibitor for CF6.
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Re-elevation of T-wave from day 2 to day 4 after successful percutaneous coronary intervention predicts chronic cardiac systolic dysfunction in patients with first anterior acute myocardial infarction2013
Author(s)
Nishizaki F, Tomita H, Yokoyama H, Higuma T, Abe N, Suzuki A, Endo T, Tateyama S, Ishida Y, Osanai T, Okumura K
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Journal Title
Heart Vessels
Volume: 28
Pages: 704-713
Related Report
Peer Reviewed
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[Journal Article] Coronary Vasospasm Induced in Transgenic Mouse with the Increased Phospholipase C-δ1 Activity.2012
Author(s)
Shibutani S, Osanai T, Ashitate T, Sagara S, Izumiyama K, Yamamoto Y, Hanada K, Echizen T, Tomita H, Fujita T, Miwa T, Matsubara H, Homma Y, Okumura K.
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Journal Title
Circulation
Volume: 125
Pages: 1027-1036
Related Report
Peer Reviewed
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[Journal Article] Overexpression of coupling factor 6 attenuates exercise-induced physiological cardiac hypertrophy by inhibiting PI3K/Akt signaling in mice.2012
Author(s)
Sagara S, Osanai T, Itoh T, Izumiyama K, Shibutani S, Hanada K, Yokoyama H, Yamamoto Y, Yokota T, Tomita H, Magota K, Okumura K.
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Journal Title
J Hypertens
Volume: 30
Pages: 778-786
Related Report
Peer Reviewed
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