| 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 |
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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 |
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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)
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| Keywords | coupling factor 6 / IF1 / ATP synthase / acidosis / HEK293 / HUVEC / intracellular acidosis / ATPase IF1 / mitochondria / prostacyclin / diabetes / hypertension / cardiac hypertrophy |
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| 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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