The effect of hypokinesia and hypodynamia on protein turnover and the growth of four skeletal muscles of the rat

Abstract

An animal suspension model has been used to simulate the weightlessness experienced during space travel. This procedure results in a reduction in the normal shortening (i.e. hypokinesia) and force generation functions of hind limb muscles (i.e. hypodynamia). The ensuing muscle atrophy was studied over 12 days in different muscle types. Slow muscles (e.g. the soleus) underwent a more pronounced atrophy than intermediate (i.e. gastrocnemius) and fast phasic muscles (e.g. extensor digitorum longus). In all muscle types inactivity resulted in a smaller accumulation of DNA and losses of RNA and protein after 5 days. The latter arose from a decrease in the rate of protein synthesis (measured in vivo) and an increase in protein breakdown. Increased specific activities of cathepsins B and D also supported the view that there is an increased proteolysis after hypokinesia and hypodynamia. When the inactive soleus was simultaneously held in a lengthened (stretched) state the atrophy was prevented through a large increase in the fractional rate of protein synthesis. Protein degradation remained elevated with stretch, thereby slowing the growth of these muscles relative to those in pair-fed, ambulatory controls. The much smaller atrophy of the tibialis anterior and extensor digitorum longus muscles in suspended only limbs represented an underestimate of the true atrophic effects of hypokinesia and hypodynamia. In this model gravity pulls the suspended foot into a plantar flexed position, thereby permanently stretching and protecting such flexor muscles. When this influence of stretch was removed a greater atrophy ensued, mainly due to the loss of the stretch-induced stimulation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

The molecular basis of skeletal muscle atrophy

“…It is well established that muscle disuse due to the removal of weight bearing leads to an early decrease in protein synthesis rate (28,64,91). While translation of an mRNA to protein occurs in phases called initiation, elongation, and termination, the first two are thought to be more highly regulated (81).…”

“…While it has been well established that muscle disuse due to the removal of weight bearing leads to an early decrease in protein synthesis and an increase in protein degradation rate (28,64,91), the upstream molecules regulating these changes are poorly defined. Figure 1 illustrates the organizational hierarchy of molecular components that may be involved in the atrophy pathway.…”

Prehabilitation: The Void in the Management of Anterior Cruciate Ligament Injuries—A Clinical Review

“…Decreased levels of physical activity [54][55][56], weightbearing status [56][57][58], and immobilization [59][60][61] can lead to progressive atrophy. Several factors including decreased protein synthesis [62][63][64], increased levels of plasma cortisol [65], arthrogenic inhibition [66,67], and altered afferent inflow [66] may be responsible for atrophy after trauma or in periods of prolonged muscular disuse. Though evidence is lacking, this notion alone supports the possible benefits of prehabilitation in preoperative ACL-deficient patients.…”

Reloading of atrophied rat soleus muscle induces tenascin-C expression around damaged muscle fibers

“…Generally, unloading causes loss of mass (atrophy) and strength in antigravitational skeletal muscles (23,29,36), whereas stimuli increasing skeletal muscle load cause opposite adaptations (1,22,30,59,69). Although increased mechanical load is known to increase skeletal muscle mass, it can also cause injury of muscle fibers, which triggers a host inflammatory response that is followed by muscle fiber regeneration (6).…”