Department of Surgery, Taichung Veterans General Hospital, Taichung 40704, Taiwan.
Department of Animal Science and Biotechnology, Tunghai University, Taichung 40704, Taiwan.
Molecules. 2021 Oct 30;26(21):6577. doi: 10.3390/molecules26216577.
Sarcopenia is an aging associated disorder involving skeletal muscle atrophy and a reduction in muscle strength, and there are no pharmaceutical interventions available thus far. Moreover, conditions such as hyperglycaemia are known to further intensify muscle degradation. Therefore, novel strategies to attenuate skeletal muscle loss are essential to enhance muscle function and thereby improve the quality of life in diabetic individuals. In this study, we have investigated the efficiency of a potato peptide hydrolysate PPH902 for its cytoprotective effects in skeletal muscle cells. PPH902 treatment in C2C12 cells showed the dose-dependent activation of the Akt/mTOR signalling pathway that is involved in skeletal myogenesis. According to Western blotting analysis, PPH902 induced the phosphorylation of Akt, mTOR proteins and induced the myogenic differentiation of C2C12 myoblasts in a differentiation medium. The phosphorylation myogenic transcription factor Foxo3A was also found to be increased in the cells treated with PPH902. In addition, treatment with PPH902 ameliorated the high glucose induced reduction in cell viability in a dose-dependent manner. Moreover, the number of myotubes in a differentiation medium reduced upon high glucose challenge, but treatment with PPH902 increased the number of differentiated myotubes. Further, the phosphorylations of AMPK and mitochondrial-related transcription factors such as PGC-1α were suppressed upon high glucose challenge but PPH902 treatment restored the protein levels. We demonstrate, for the first time, that a specific potato peptide has a therapeutic effect against sarcopenia. In addition, PPH902 improved the myogenic differentiation and their mitochondrial biogenesis and further improved myogenic protein and inhibited muscle protein degradation in C2C12 cells challenged under a high glucose condition.
肌肉减少症是一种与衰老相关的疾病，涉及骨骼肌萎缩和肌肉力量下降，目前尚无药物干预措施。此外，高血糖等情况已知会进一步加剧肌肉降解。因此，需要采取新的策略来减轻骨骼肌的损失，以增强肌肉功能，从而提高糖尿病患者的生活质量。在这项研究中，我们研究了马铃薯肽水解物 PPH902 对骨骼肌细胞的细胞保护作用的效率。PPH902 处理 C2C12 细胞显示出 Akt/mTOR 信号通路的剂量依赖性激活，该通路参与骨骼肌生成。根据 Western blot 分析，PPH902 诱导 Akt、mTOR 蛋白的磷酸化，并在分化培养基中诱导 C2C12 成肌细胞的肌生成分化。还发现用 PPH902 处理的细胞中磷酸化的肌生成转录因子 Foxo3A 增加。此外，PPH902 以剂量依赖性方式改善高葡萄糖诱导的细胞活力降低。此外，在高葡萄糖挑战下，分化培养基中的肌管数量减少，但用 PPH902 处理会增加分化的肌管数量。此外，高葡萄糖挑战会抑制 AMPK 的磷酸化和与线粒体相关的转录因子（如 PGC-1α）的磷酸化，但 PPH902 处理会恢复蛋白质水平。我们首次证明，特定的马铃薯肽对肌肉减少症具有治疗作用。此外，PPH902 改善了 C2C12 细胞在高葡萄糖条件下的成肌分化及其线粒体生物发生，并进一步改善了肌生成蛋白并抑制了肌肉蛋白降解。
