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.
Highlights
In both space physiology and rehabilitation medicine, it is critical to develop new effective exercise and pharmacological countermeasures in order to attenuate/prevent disuse-induced skeletal muscle atrophy as well as to enhance skeletal muscle recovery following a long period of inactivity
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 mechanistic target of rapamycin complex 1 (mTORC1) following HU
Soleus weight to body weight ratio significantly decreased by 16% (p < 0.05) after 7-day HS compared with the control animals
Summary
In both space physiology and rehabilitation medicine, it is critical to develop new effective exercise and pharmacological countermeasures in order to attenuate/prevent disuse-induced skeletal muscle atrophy as well as to enhance skeletal muscle recovery (regrowth) following a long period of inactivity. In order to understand how mechanical stimuli regulate muscle mass, it is important to comprehend how skeletal muscles sense mechanical signals and convert them into biochemical events (mechanotransduction) regulating the rate of protein synthesis (PS). It is well-established that mammalian/mechanistic target of rapamycin complex 1 (mTORC1) plays a key role in the regulation of skeletal muscle PS and muscle mass in response to mechanical stimuli [2,3,4,5]. The aims of the present study were (i) to evaluate a temporal response of anabolic signaling and protein synthesis (PS) to a bout of EC in the rat soleus at different time points of mechanical unloading and (ii) to assess a possible role of SAC in the propagation of a mechanical signal to mTORC1 in the soleus muscle following hindlimb unloading (HU)
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