An Anabolic Signaling Response of Rat Soleus Muscle to Eccentric Contractions Following Hindlimb Unloading: A Potential Role of Stretch-Activated Ion Channels

Int J Mol Sci. 2019 Mar 7;20(5):1165. doi: 10.3390/ijms20051165.

Abstract

Mechanisms that convert a mechanical signal into a biochemical response in an atrophied skeletal muscle remain poorly understood. The aims of the study were to evaluate a temporal response of anabolic signaling and protein synthesis (PS) to eccentric contractions (EC) in rat soleus during hindlimb unloading (HU); and to assess a possible role of stretch-activated ion channels (SAC) in the propagation of a mechanical signal to mTORC1 following HU. Following HU, an isolated soleus was subjected to EC. Upon completion of EC, muscles were collected for western blot analyses to determine the content/phosphorylation of the key anabolic markers. We found that a degree of EC-induced p70S6K phosphorylation and the rate of PS in the soleus of 3- and 7-day unloaded rats was significantly less than that in control. A decrease in EC-induced phosphorylation of p70S6K, RPS6 and PS in the 7-day unloaded soleus treated with SAC inhibitor did not differ from that of the 7-day unloaded soleus without SAC blockade. The results of the study suggest that (i) HU results in a blunted anabolic response to a bout of EC, (ii) attenuation of mTORC1-signaling and PS in response to EC in unloaded soleus may be associated with inactivation of SAC.

Keywords: anabolic signaling; eccentric contractions; hindlimb unloading; protein synthesis; soleus muscle; stretch-activated channels.

MeSH terms

  • Animals
  • Body Weight
  • Disease Models, Animal
  • Hindlimb Suspension / adverse effects*
  • Hindlimb Suspension / methods
  • Male
  • Muscle Contraction
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism*
  • Phosphorylation
  • Rats
  • Ribosomal Protein S6 / metabolism*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction

Substances

  • Muscle Proteins
  • Ribosomal Protein S6
  • Ribosomal Protein S6 Kinases, 70-kDa