| 研究課題/領域番号 |
18K14407
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| 研究機関 | 広島大学 |
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研究代表者 |
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| 研究期間 (年度) |
2018-04-01 – 2021-03-31
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| キーワード | Homocarnosine / GABA / Skeletal muscle / Carnosine |
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| 研究実績の概要 |
We finished the first step of finding food factors enhancing endogenous homocarnosine synthesis in skeletal muscle. We found that dietary γ-aminobutyric acid (GABA) significantly increased homocarnosine levels (50-folds) in skeletal muscle. We hypothesized that GABA-degradating enzyme (GABA transaminase (GABA-T)) regulates intracellular GABA levels and affects the synthesis of homocarnosine in skeletal muscle. Thus, the enzyme inhibitor vig (Vig) was injected into mice. We found that Vig significantly inhibited GABA-T activity in liver and increased GABA and homocarnosine levels in skeletal muscle. Interestingly, Vig injection significantly increased GABA and homocarnosine levels in brain. For in vitro homocarnosine synthesis, the chemical synthesis protocol is already established.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Currently, the research has progressed smoothly as planed. We could early establish the LC-MS method for detecting trace concentration of homocarnosine, which made the research progress smoothly. For producing large amount of homocarnosine for animal experiment in FY 2020, we struggled with over-expressing carnosine synthase in E.Coli. Thus, we changed to use the Fmoc solid-phase synthesis of homocarnosine instead and successfully established the protocol.
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| 今後の研究の推進方策 |
In FY 2019, synthesizing homocarnosine will be continued. Physiological effects of dietary GABA on skeletal muscle will be tested. GABA diet will be given to mice, then tibialis anterior (TA) muscle will be injured by injection of cardiotoxin. The effects of dietary GABA on muscle regeneration will be examined by histochemical and immunofluorescence analyses. Satellite cells or muscle stem cells will also be examined. This muscle regeneration experiment will be started from June, 2019.
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| 次年度使用額が生じた理由 |
Since we could find the potent food factor (GABA) inducing homocarnosine synthesis in skeletal muscle earlier than we thought, we could reduce a number of experiments. Thus, the usage of the budget was lower than planned. Instead of reducing a number of experiments in FY 2018, I have made up an additional experiment plan in FY 2019. In FY 2019, I will establish the mouse model for muscle regeneration to see if dietary GABA can help muscle to regenerate faster after damage. The establishment of this model is expected to cause much money on animals and cardiotoxin (an expensive chemical). Thus, the left amount of money (405,632 yen) will be used for the model establishment in this FY 2019.
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