CarMeN Laboratory, INSERM, INRA, University of Lyon, Pierre-Benite, France.
Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000, Strasbourg, France.
Sci Rep. 2018 Apr 3;8(1):5525. doi: 10.1038/s41598-018-23891-5.
Muscle atrophy is one of the main characteristics of human ageing and physical inactivity, with resulting adverse health outcomes. To date, there are still no efficient therapeutic strategies for its prevention and/or treatment. However, during hibernation, bears exhibit a unique ability for preserving muscle in conditions where muscle atrophy would be expected in humans. Therefore, our objective was to determine whether there are components of bear serum which can control protein balance in human muscles. In this study, we exposed cultured human differentiated muscle cells to bear serum collected during winter and summer periods, and measured the impact on cell protein content and turnover. In addition, we explored the signalling pathways that control rates of protein synthesis and degradation. We show that the protein turnover of human myotubes is reduced when incubated with winter bear serum, with a dramatic inhibition of proteolysis involving both proteasomal and lysosomal systems, and resulting in an increase in muscle cell protein content. By modulating intracellular signalling pathways and inducing a protein sparing phenotype in human muscle cells, winter bear serum therefore holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders.
肌肉萎缩是人类衰老和身体不活动的主要特征之一，会导致健康状况恶化。迄今为止，仍然没有有效的预防和/或治疗方法。然而，在冬眠期间，熊表现出一种独特的能力，可以在人类肌肉萎缩预期的情况下保持肌肉。因此，我们的目的是确定熊血清中是否有可以控制人体肌肉中蛋白质平衡的成分。在这项研究中，我们将培养的人类分化肌肉细胞暴露于冬季和夏季采集的熊血清中，并测量对细胞蛋白质含量和周转率的影响。此外，我们还探讨了控制蛋白质合成和降解速度的信号通路。我们发现，当用冬季熊血清孵育时，人类肌管的蛋白质周转率降低，涉及蛋白酶体和溶酶体系统的蛋白水解明显受到抑制，导致肌肉细胞蛋白质含量增加。通过调节细胞内信号通路并在人类肌肉细胞中诱导蛋白质节约表型，冬季熊血清因此有可能开发新的工具来对抗人类肌肉萎缩和相关代谢紊乱。
