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.NEW & NOTEWORTHY 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.
Keywords: hindlimb unloading; muscle atrophy; ribophagy; ribosome biogenesis; ribosome synthesis.