Investigation of the role of branched chain amino add on stimulation of protein synthesis and application for preservation and improvement of muscle mass
| Project/Area Number |
18500509
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Sports science
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
NAKAI Naoya Osaka University, Graduate School of Medicine, Assistant Professor (90324508)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | branched-chain amino acid / leucine / protein synthesis / skeletal muscle / RNA interference / BCKDH / p70 S6 kinase |
|---|
| Research Abstract |
Branched-chain amino acid Ieucine has been shown to activate the protein translational regulators. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the ranched-chain α-keto acid dehydrogenase (BCKDH) complex. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The results demonstrated that knockdown of the BCKDH E2 subunit expression, presumably abolishing the BCKDH complex activity, increased the effect of leucine on phosphorylation of p70S6K, a key regulatory protein involved in the initiation of mRNA translation. On the contrary, activation of BCKDH complex by trancfection of kinase-siRNA decreased the leucine's effect. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex. It has been reported that BCKDH activity in liver has gender difference. So we investigated the leucine-induced activation of the protein translation initiation in male and female rats. Leucien-induced activation of the translation initiation in skeletal muscle was increased both in male and female rats at the end of light period (hepatic BDKCH activity is higher in male rats than female rats). In contrast, leucine-induced activation of the translation initiation in skeletal muscle was higher in male rats than female rats after the 18 h starvation (hepatic BCKDH is inactivated both in male and female rats). These results suggest that gender difference in leucine-induced activation of the protein translation initiation in skeletal muscle is not related to the activity of hepatic BCKDH. Further studies are needed to elucidate the gender difference in leucine-induced activation of the protein translation initiation.
|
Report
(3 results)
Research Products
(15 results)
-
[Journal Article] Role(s) of nucleoli, phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass.2007
Author(s)
Kawano, F,. Matsuoka, Y., Oke, Y., Higo, Y., Terada, M., Wang, X., Nakai, N., Fukuda, H., Ohmi, S., and Ohira, Y.
-
Journal Title
Am. J. Physiol. Cell Physiol. 293
Related Report
Peer Reviewed
-
-
-
[Journal Article] Leucine-induced activation of translational initiation is partly regulated by the branched-chain α-keto acid dehydrogenase complex in C2C12 cells2006
Author(s)
Nakai, N., Shimomura, Y., Tamura, T., Tamura, N., Hamada, K., Kawano, F., Ohira, Y
-
Journal Title
Biochem. Biophys. Res. Commun 343
Pages: 1244-1250
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
[Presentation] Peroxisome proliferators-activated receptor α (PPARα) agonist, WY-14,643, increased leucine-induced activation of translation initiation in C2C12 cells2007
Author(s)
Nakai, N., Kawano, F., Tenth, M., Ohira, Y
Organizer
12th International congress of World Muscle Society
Place of Presentation
Messina, Sicily, Itary
Year and Date
2007-10-09
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
[Presentation] Activation of the p70 S6 kinase by leucine is partly regulated by the activity of branched-chain α-keto acid dehydrogenase(BCKDH)complex2006
Author(s)
Nakai, N., Shimomura, Y., Tamura, T., Tamura, N., Hamada, K., Kawano, F., and Ohira, Y.
Organizer
Experimental Biology 2006
Place of Presentation
San Francisco, California
Year and Date
2006-04-02
Description
「研究成果報告書概要(和文)」より
Related Report
-
[Presentation] Activation of the p70 S6 kinase by leucine is partly regulated by the activity of branched-chain a-keto acid dehydrogenase (BCKDH) complex2006
Author(s)
Nakai, N., Shimomura, Y., Tamura, T., Tamura, N., Hamada, K., Kawano, F., Ohira, Y
Organizer
Experimental Biology 2006
Place of Presentation
San Francisco, California
Year and Date
2006-04-02
Description
「研究成果報告書概要(欧文)」より
Related Report
