AMP-activated Protein Kinase Activation Suppresses Protein Synthesis and mTORC1 Signaling in Chick Myotube Cultures.
AMP-activated Protein Kinase Activation Suppresses Protein Synthesis and mTORC1 Signaling in Chick Myotube Cultures.
复制标题
DOI：
10.2141/jpsa.0210021
复制
发表时间：
2022-01-25
期刊：
影响因子：
--
通讯作者：
Ishida A
中科院分区：
文献类型：
--
作者：
Nakashima K;Ishida A
骨骼肌中的蛋白质合成被认为是最耗能的细胞过程之一。AMP活化蛋白激酶（AMPK）是调节糖和脂质代谢的代谢主开关，并且其涉及骨骼肌中蛋白质合成控制。雷帕霉素复合物1（mTORC 1）的机制靶标是细胞中蛋白质代谢的中心调节剂。然而，AMPK激活对鸡骨骼肌中蛋白质合成和mTORC 1信号转导的影响仍不清楚。因此，在本研究中，我们旨在研究AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）对鸡肌管培养物中蛋白质合成和mTORC 1信号转导的影响。鸡肌管与AICAR（1 mM）孵育3小时导致AMPK（Thr 172）磷酸化的显着增加。尽管如此，蛋白质合成，使用翻译方法的表面传感测量，显着降低AICAR。此外，AICAR显著降低了p70核糖体S6激酶1（S6 K1，Thr 389）、S6核糖体蛋白（Ser 240/244）和真核翻译起始因子4 E结合蛋白1（4 E-BP 1，Thr 37/46）的磷酸化。这些结果表明，AMPK激活抑制蛋白质合成和mTORC 1信号（通过磷酸化的S6 K1，S6核糖体蛋白，和4 E-BP 1）在鸡肌管。
Protein synthesis in skeletal muscle is considered one of the most energy-consuming cellular processes. AMP-activated protein kinase (AMPK) is a metabolic master switch that regulates glucose and lipid metabolism, and it is implicated in protein synthesis control in skeletal muscles. The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of protein metabolism in cells. However, the effect of AMPK activation on protein synthesis and mTORC1 signaling in chicken skeletal muscle remains unclear. Therefore, in this study, we aimed to investigate the effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMPK activator, on protein synthesis and mTORC1 signaling in chick myotube cultures. The incubation of chick myotubes with AICAR (1 mM) for 3 h led to a significant increase in AMPK (Thr172) phosphorylation. Nonetheless, protein synthesis, measured using the surface sensing of translation method, was significantly decreased by AICAR. In addition, the phosphorylation of p70 ribosomal S6 kinase 1 (S6K1, Thr389), S6 ribosomal protein (Ser240/244), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1, Thr37/46) was significantly reduced by AICAR. These results suggest that AMPK activation suppresses protein synthesis and mTORC1 signaling (through the phosphorylation of S6K1, S6 ribosomal protein, and 4E-BP1) in chick myotubes.