| Project/Area Number |
23700832
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied health science
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| Research Institution | Kobe University |
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Principal Investigator |
UEDA Shuji 神戸大学, (連合)農学研究科(研究院), 助教 (50379400)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 加齢 / 老化 / RhoA / IGF-I / 筋肉 / DGK / heat shock protein / BirA / C2C12 / RhoGDI / グアニンヌクレオチド交換因子 / GTP加水分解活性化タンパク質 / GEF / Myostatin |
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| Outline of Final Research Achievements |
Rho family GTPase RhoA has been known to be involved in the muscular development and reconstruction. However, the role of RhoA in IGF-1-induced muscular hypertrophy remain to be revealed. To investigate the regulatory mechanism of RhoA activation, we used muscular hypertrophy model of C2C12 cells. After IGF-I treatment, protein level of RhoA was upregulated, and activated RhoA was continuously increased in hypertrophic myotubes.RhoA dominant-negative mutant impaired prominent hypertrophy, and inhibited IGF-1-depending p38 MAPK activation and M-cadherin-shift, which are required for muscular differentiation.These results indicate that RhoA involves in multiple steps of IGF-I-induced muscular hypertrophy. To identify the key molecule in this mechanism, we designed RhoA tagged with promiscuous biotin ligase BirA and isolated several interesting RhoA binding candidate.
This study clarified one end of the activation mechanism of RhoA related to muscular hypertrophy by IGF-1.
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