Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway.
Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway.
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琥珀酸通过 Erk1/2 信号通路促进骨骼肌蛋白合成
DOI：
10.3892/mmr.2017.7554
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发表时间：
2017-11
影响因子：
3.4
通讯作者：
Shu G
中科院分区：
文献类型：
--
作者：
Yuan Y;Xu Y;Xu J;Liang B;Cai X;Zhu C;Wang L;Wang S;Zhu X;Gao P;Wang X;Zhang Y;Jiang Q;Shu G
众所周知，耐力训练对减轻骨骼肌萎缩是有效的。琥珀酸酯是一种典型的三氯乙酸代谢物，运动可显著增加其含量。本研究旨在研究琥珀酸对骨骼肌蛋白质合成的影响，并试图阐明其可能的机制。体外研究发现，琥珀酸可剂量依赖性地促进C2C12肌管蛋白合成，并增强AKT丝氨酸/苏氨酸激酶1(Akt)、雷帕霉素靶标S6、真核翻译起始因子4E、4E结合蛋白1和叉头盒O(FoxO)3a的磷酸化水平。此外，20 mM琥珀酸能显著增加细胞内[Ca~(2+)]i，继而使磷酸化细胞外调节激酶(Erk)、-Akt水平及Erk和Akt之间的串扰增加。值得注意的是，ERK拮抗剂(U0126)或mTOR抑制剂(雷帕霉素)可阻断琥珀酸对蛋白质合成的影响。体内研究证实，琥珀酸除使ERK、Akt和FOXO3a的磷酸化水平升高外，还呈剂量依赖性地增加腓肠肌的蛋白质合成。综上所述，这些发现表明琥珀酸通过ERK/Akt信号通路促进骨骼肌蛋白质沉积。
It is well known that endurance training is effective to attenuate skeletal muscle atrophy. Succinate is a typical TCA metabolite, of which exercise could dramatically increase the content. The present study aimed to investigate the effect of succinate on protein synthesis in skeletal muscle, and try to delineate the underlying mechanism. The in vitro study revealed that succinate dose-dependently increased protein synthesis in C2C12 myotube along with the enhancement of phosphorylation levels of AKT Serine/Threonine Kinase 1(Akt), mammalian target of rapamycin, S6, eukaryotic translation initiation factor 4E, 4E binding protein 1 and forkhead box O (FoxO) 3a. Furthermore, it was demonstrated that 20 mM succinate markedly increased [Ca2+]i. Then, the phospho-extracellular regulated kinase (Erk), -Akt level and the crosstalk between Erk and Akt were elevated in response to succinate. Notably, the Erk antagonist (U0126) or mTOR inhibitor (rapamycin) abolished the effect of succinate on protein synthesis. The in vivo study verified that succinate dose-dependently increased the protein synthesis, in addition to phosphorylation levels of Erk, Akt and FoxO3a in gastrocnemius muscle. In summary, these findings demonstrated that succinate promoted skeletal muscle protein deposition via Erk/Akt signaling pathway.
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