亮氨酸在马骨骼肌卫星细胞中通过 AMPK/mTOR 信号促进能量代谢并刺激慢速肌纤维的表达

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Jingya Xing , Gerelchimeg Bou , Guiqin Liu , Xinyu Li , Yingchao Shen , Muhammad Faheem Akhtar , Dongyi Bai , Yiping Zhao , Manglai Dugarjaviin , Xinzhuang Zhang
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引用次数: 0

摘要

以往的研究表明,亮氨酸(Leucine,Leu)可以刺激和增强马骨骼肌卫星细胞(SCs)的增殖。与亮氨酸诱导的马骨骼肌卫星细胞增殖相关的基因表达谱也已记录在案。然而,Leu 在调节马骨骼肌卫星细胞中慢肌纤维(slow-MyHC)的表达和线粒体功能方面的具体作用及其内在机制仍不清楚。在这项研究中,马SCs在分化培养基中进行培养,并在3天内接受不同浓度的Leu(0毫摩尔、0.5毫摩尔、1毫摩尔、2毫摩尔、5毫摩尔和10毫摩尔)。我们利用 AMP 激活蛋白激酶(AMPK)抑制剂化合物 C 和哺乳动物雷帕霉素复合体靶标(mTOR)抑制剂雷帕霉素来探索其潜在机制。结果表明,在2 mM的Leu水平下,慢-MyHC的表达量显著高于0 mM、0.5 mM和10 mM的水平(P <0.01),与其他组相比无显著差异(P >0.05);基础呼吸、最大呼吸、待机呼吸以及慢-MyHC、PGC-1α、Cytc、ND1、TFAM和COX1的表达量均随Leu的补充而显著增加(P <0.01)。我们还发现,Leu 上调了 AMPK 和 mTOR 信号通路上关键蛋白的表达,包括 LKB1、p-LKB1、AMPK、p-AMPK、S6、p-S6、4EBP1、p-4EBP1、mTOR 和 p-mTOR(P < 0.05 或 P < 0.01)。值得注意的是,当我们用AMPK抑制剂化合物C和mTOR抑制剂雷帕霉素处理马SCs时,我们观察到Leu对慢MyHC相关基因表达和信号通路相关基因表达的有益作用有所降低。本研究提供了新的证据,证明 Leu 可通过 AMPK/mTOR 信号通路促进马 SCs 的慢-MyHC 表达并增强线粒体功能,首次揭示了这些过程的内在机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Leucine promotes energy metabolism and stimulates slow-twitch muscle fibers expression through AMPK/mTOR signaling in equine skeletal muscle satellite cells

Leucine promotes energy metabolism and stimulates slow-twitch muscle fibers expression through AMPK/mTOR signaling in equine skeletal muscle satellite cells

Previous research has shown that leucine (Leu) can stimulate and enhance the proliferation of equine skeletal muscle satellite cells (SCs). The gene expression profile associated with Leu-induced proliferation of equine SCs has also been documented. However, the specific role of Leu in regulating the expression of slow-twitch muscle fibers (slow-MyHC) and mitochondrial function in equine SCs, as well as the underlying mechanism, remains unclear. During this investigation, equine SCs underwent culturing in differentiation medium and were subjected to varying concentrations of Leu (0 mM, 0.5 mM, 1 mM, 2 mM, 5 mM, and 10 mM) over a span of 3 days. AMP-activated protein kinase (AMPK) inhibitor Compound C and mammalian target of rapamycin complex (mTOR) inhibitor Rapamycin were utilized to explore its underlying mechanism. Here we showed that the expression of slow-MyHC at 2 mM Leu level was significantly higher than the concentration levels of 0 mM,0.5 mM and 10 mM (P <0.01), and there was no significant difference compared to other groups (P > 0.05); the basal respiration, maximum respiration, standby respiration and the expression of slow-MyHC, PGC-1α, Cytc, ND1, TFAM, and COX1 were significantly increased with Leu supplementation (P < 0.01). We also found that Leu up-regulated the expression of key proteins on AMPK and mTOR signaling pathways, including LKB1, p-LKB1, AMPK, p-AMPK, S6, p-S6, 4EBP1, p-4EBP1, mTOR and p-mTOR (P < 0.05 or P < 0.01). Notably, when we treated the equine SCs with the AMPK inhibitor Compound C and the mTOR inhibitor Rapamycin, we observed a reduction in the beneficial effects of Leu on the expression of genes related to slow-MyHC and signaling pathway-related gene expressions. This study provides novel evidence that Leu promotes slow-MyHC expression and enhances mitochondrial function in equine SCs through the AMPK/mTOR signaling pathways, shedding light on the underlying mechanisms involved in these processes for the first time.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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