Nakanishi Ryosuke, Tanaka Minoru, Maeshige Noriaki, Kondo Hiroyo, Roy Roland R, Fujino Hidemi
Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan.
Department of Physical Therapy, Faculty of Rehabilitation, Kobe International University, Kobe, Hyogo, Japan.
Exp Physiol. 2021 Jul;106(7):1587-1596. doi: 10.1113/EP089337. Epub 2021 May 20.
What is the central question of this study? The purpose of this study was to determine whether the nucleotides in a nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in soleus muscle mass and fibre size. What is the main finding and its importance? The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy.
Hindlimb unloading decreases both the protein synthesis pathway and satellite cell activation and results in muscle atrophy. Nucleotides are included in nucleoprotein and provide the benefits of increasing extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. ERK1/2 phosphorylation is also important in the activation of satellite cells, especially for myoblast proliferation and stimulating protein synthesis pathways. Therefore, we hypothesized that nucleotides in the nucleoproteins would ameliorate muscle atrophy by increasing the protein synthesis pathways and satellite cell activation during hindlimb unloading in rat soleus muscle. Twenty-four female Wistar rats were divided into four groups: control rats fed a basal diet without nucleoprotein (CON), control rats fed a nucleoprotein-enriched diet (CON+NP), hindlimb-unloaded rats fed a basal diet (HU) or hindlimb-unloaded rats fed a nucleoprotein-enriched diet (HU+NP). HU for 2 weeks resulted in reductions in phosphorylation of p70S6K and rpS6, the numbers of myoblast determination protein (MyoD)- and myogenin- positive nuclei, type I muscle fibre size and muscle mass. Both CON+NP and HU+NP rats showed an increase in ERK1/2, phosphorylation of p70S6K and rpS6, and the numbers of MyoD- and myogenin-positive nuclei compared with their basal diet groups. The NP diet also ameliorated the unloading-associated decrease in type I muscle fibre size and muscle mass. The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy.
本研究的核心问题是什么？本研究的目的是确定富含核蛋白的饮食中的核苷酸是否能改善因失重导致的比目鱼肌肌肉质量和纤维大小的减少。主要发现及其重要性是什么？结果表明，富含核蛋白的饮食中的核苷酸可以改善因失重导致的I型纤维大小和肌肉质量的减少，这很可能是由于通过细胞外信号调节激酶1/2（ERK1/2）磷酸化激活了蛋白质合成途径以及卫星细胞的增殖和分化。因此，补充核苷酸似乎是对抗肌肉萎缩的一种有效对策。
后肢卸载会降低蛋白质合成途径以及卫星细胞的激活，并导致肌肉萎缩。核苷酸包含在核蛋白中，具有增加细胞外信号调节激酶（ERK）1/2磷酸化的作用。ERK1/2磷酸化在卫星细胞的激活中也很重要，特别是对于成肌细胞增殖和刺激蛋白质合成途径而言。因此，我们假设核蛋白中的核苷酸会通过在后肢卸载期间增加大鼠比目鱼肌的蛋白质合成途径和卫星细胞激活来改善肌肉萎缩。将24只雌性Wistar大鼠分为四组：喂食不含核蛋白的基础饮食的对照大鼠（CON）、喂食富含核蛋白饮食的对照大鼠（CON+NP）、喂食基础饮食的后肢卸载大鼠（HU）或喂食富含核蛋白饮食的后肢卸载大鼠（HU+NP）。后肢卸载2周导致p70S6K和rpS6的磷酸化减少、成肌细胞决定蛋白（MyoD）和肌细胞生成素阳性核的数量减少、I型肌纤维大小和肌肉质量减少。与喂食基础饮食的组相比，CON+NP组和HU+NP组大鼠均表现出ERK1/2增加、p70S6K和rpS6磷酸化增加以及MyoD和肌细胞生成素阳性核的数量增加。富含核蛋白的饮食也改善了因卸载导致的I型肌纤维大小和肌肉质量的减少。结果表明，富含核蛋白的饮食中的核苷酸可以改善因失重导致的I型纤维大小和肌肉质量的减少，这很可能是由于通过ERK1/2磷酸化激活了蛋白质合成途径以及卫星细胞的增殖和分化。因此，补充核苷酸似乎是对抗肌肉萎缩的一种有效对策。
