Research Institute for Sport Science, Nippon Sport Science University, Tokyo, Japan.
Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan.
J Appl Physiol (1985). 2022 Oct 1;133(4):822-833. doi: 10.1152/japplphysiol.00204.2022. Epub 2022 Aug 25.
Skeletal muscle unloading leads to muscle atrophy. Ribosome synthesis has been implicated as an important skeletal muscle mass regulator owing to its translational capacity. Muscle unloading induces a reduction in ribosome synthesis and content, with muscle atrophy. Percutaneous electrical muscle stimulation (pEMS)-induced muscle contraction is widely used in clinics to improve muscle mass. However, its efficacy in rescuing the reduction in ribosomal synthesis has not been addressed thus far. We examined the effects of daily pEMS treatment on ribosome synthesis and content during mouse hindlimb unloading. Male C57BL/6J mice were randomly assigned to sedentary (SED) and hindlimb unloading by pelvic suspension (HU) groups. Muscle contraction was triggered by pEMS treatment of the right gastrocnemius muscle of a subset of the HU group (HU + pEMS). Hindlimb unloading for 6 days significantly lowered 28S rRNA, rpL10, and rpS3 expression, which was rescued by daily pEMS treatment. The protein expression of phospho-p70S6K and UBF was significantly higher in the HU + pEMS than in the HU group. The mRNA expression of ribophagy receptor Nufip1 increased in both the HU and HU + pEMS groups. Protein light chain 3 (LC3)-II expression and the LC3-II/LC3-I ratio were increased by HU, but pEMS attenuated this increase. Our findings indicate that during HU, daily pEMS treatment prevents the reduction in the levels of some proteins associated with ribosome synthesis. In addition, the HU-induced activation of ribosome degradation may be attenuated. These data provide insights into ribosome content regulation and the mechanism of attenuation of muscle atrophy by pEMS treatment during muscle disuse. Muscle inactivity reduces ribosome synthesis and content during atrophy. Whether percutaneous electrical muscle stimulation (pEMS)-induced muscle contraction rescues the ribosome synthesis and content during muscle unloading is unclear. Using a mouse hindlimb-unloading model with pelvic suspension, we provide evidence that daily pEMS-induced muscle contraction during hindlimb unloading rescues the reduction in the expression of some ribosome synthesis-related proteins and ribosome content in the gastrocnemius muscle.
骨骼肌废用导致肌肉萎缩。核糖体合成因其翻译能力而被认为是调节骨骼肌质量的重要因素。肌肉废用导致核糖体合成和含量减少,进而导致肌肉萎缩。经皮电肌肉刺激(pEMS)诱导的肌肉收缩广泛应用于临床以改善肌肉质量。然而,其在挽救核糖体合成减少方面的疗效尚未得到解决。我们研究了每天进行 pEMS 治疗对小鼠后肢去负荷时核糖体合成和含量的影响。雄性 C57BL/6J 小鼠被随机分配到安静(SED)和后肢去负荷(HU)组。HU 组的一部分肌肉通过 pEMS 治疗触发肌肉收缩(HU + pEMS)。后肢去负荷 6 天显著降低了 28S rRNA、rpL10 和 rpS3 的表达,而每天进行 pEMS 治疗可挽救这种降低。HU + pEMS 组的磷酸化 p70S6K 和 UBF 蛋白表达明显高于 HU 组。HU 和 HU + pEMS 组的核糖体吞噬受体 Nufip1 的 mRNA 表达均增加。HU 增加了蛋白轻链 3(LC3)-II 的表达和 LC3-II/LC3-I 比值,但 pEMS 减弱了这种增加。我们的研究结果表明,在 HU 期间,每天进行 pEMS 治疗可防止与核糖体合成相关的一些蛋白质水平降低。此外,HU 诱导的核糖体降解的激活可能被减弱。这些数据为核糖体含量调节以及 pEMS 治疗在肌肉失用期间减轻肌肉萎缩的机制提供了见解。肌肉失用导致萎缩过程中核糖体合成和含量减少。经皮电肌肉刺激(pEMS)诱导的肌肉收缩是否在肌肉失用期间挽救核糖体合成和含量尚不清楚。我们使用后肢悬吊的小鼠后肢去负荷模型,提供了证据表明,每天进行 pEMS 诱导的肌肉收缩可在去负荷时挽救比目鱼肌中一些与核糖体合成相关的蛋白质表达和核糖体含量的降低。