Abstract
It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Although the exact mechanisms are unknown, a role for Ca2+ dysregulation has been suggested. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump actively brings cytosolic Ca2+ into the SR, eliciting muscle relaxation and maintaining low intracellular Ca2+ ([Ca2+]i). SERCA dysfunction contributes to elevations in [Ca2+]i, leading to cellular damage, and may contribute to the muscle weakness and atrophy observed with spaceflight. Here, we investigated SERCA function, SERCA regulatory protein content, and reactive oxygen/nitrogen species (RONS) protein adduction in murine skeletal muscle after 35–37 days of spaceflight. In male and female soleus muscles, spaceflight led to drastic impairments in Ca2+ uptake despite significant increases in SERCA1a protein content. We attribute this impairment to an increase in RONS production and elevated total protein tyrosine (T) nitration and cysteine (S) nitrosylation. Contrarily, in the tibialis anterior (TA), we observed an enhancement in Ca2+ uptake, which we attribute to a shift towards a faster muscle fiber type (i.e., increased myosin heavy chain IIb and SERCA1a) without elevated total protein T-nitration and S-nitrosylation. Thus, spaceflight affects SERCA function differently between the soleus and TA.
Highlights
It is well established that microgravity exposure during spaceflight comes with a great deal of physiological and psychosocial challenges that can compromise astronaut health [1,2,3]
Assessment of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) function in the Research 9 (RR9) soleus demonstrates that spaceflight caused significant impairments in the amount of ATP-dependent Ca2+
Similar to the data obtained from male mice from the RR9 mission (Figure 1), we found that SERCA function was impaired with a significant reduction in Ca2+ uptake compared with GC/VIV (Figure 2A,B)
Summary
It is well established that microgravity exposure during spaceflight comes with a great deal of physiological and psychosocial challenges that can compromise astronaut health [1,2,3]. Loss of muscle mass and strength is an important factor that can impede the astronaut’s ability to perform mission-related duties during space travel and upon return to Earth or partial gravity (i.e., Moon or Mars). Mammals (i.e., humans and rodents) have evolved with the never-ending downward pull of gravity on Earth, and postural muscles such as the soleus are known to be most affected with spaceflight. Similar to unloading models on Earth, spaceflight and microgravity exposure in rodents unloads the postural soleus causing extensive muscle atrophy and a fiber-type shift from slowoxidative to fast-glycolytic [4,5,6,7,8,9]. Similar changes have been observed in human soleus muscles after 17 days of spaceflight [10]. A recent study highlights the fact that skeletal muscle unloading causes disproportionate losses in muscle mass and strength, with the decline in muscle strength occurring at a faster rate than muscle mass [11]
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