Abstract
A mammalian soleus muscle along with other “axial” muscles ensures the stability of the body under the Earth’s gravity. In rat experiments with hindlimb suspension, zero-gravity parabolic flights as well as in human dry immersion studies, a dramatic decrease in the electromyographic (EMG) activity of the soleus muscle has been repeatedly shown. Most of the motor units of the soleus muscle convert from a state of activity to a state of rest which is longer than under natural conditions. And the state of rest gradually converts to the state of disuse. This review addresses a number of metabolic events that characterize the earliest stage of the cessation of the soleus muscle contractile activity. One to three days of mechanical unloading are accompanied by energy-dependent dephosphorylation of AMPK, accumulation of the reactive oxygen species, as well as accumulation of resting myoplasmic calcium. In this transition period, a rapid rearrangement of the various signaling pathways occurs, which, primarily, results in a decrease in the rate of protein synthesis (primarily via inhibition of ribosomal biogenesis and activation of endogenous inhibitors of mRNA translation, such as GSK3β) and an increase in proteolysis (via upregulation of muscle-specific E3-ubiquitin ligases).
Highlights
As a significant decrease in AMPK phosphorylation was previously detected in rat soleus muscle after 24 h of hindlimb unloading [33], we proposed a hypothesis linking the early decrease in myosin heavy chain (MyHC) I(β) expression to AMPK dephosphorylation and subsequent histone deacetylase-4 (HDAC4) dephosphorylation and nuclear import
These molecular events lead to a decrease in the rate of protein synthesis and an increase in proteolysis
There is some evidence to suggest that alternations in the concentrations of substrates and products of the routine muscle activity may serve as signals that trigger signaling rearrangements when muscle activity is ceased
Summary
A mammalian soleus is a very active muscle. It is active for at least 11 h a day [1]. Under conditions of human dry immersion, an electrical (and, mechanical) activity of the soleus muscle can be significantly increased if mechanical pressure (mechanical stimulation) is applied to the foot [5,6] This demonstrates that even when the axial loading is dramatically diminished, the influence of support on the foot can maintain a contractile activity of this muscle. A decrease in protein synthesis by more than 40% and more than a twofold decrease in the content of 18S and 28S ribosomal RNAs are demonstrated in rat soleus following 24-h unloading [14] These events are accompanied by a significant reduction in the expression of myh gene encoding slow isoform of myosin heavy chains (MyHC I (β)) [15,16]. These metabolic events will be linked in a way to present a logical and consistent picture that would allow readers to see the sequence of signaling reactions and to identify the atrophic pattern of this chain of regulatory events
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