Abstract
Microgravity induces skeletal muscle atrophy, particularly in the soleus muscle, which is predominantly composed of slow-twitch myofibre (type I) and is sensitive to disuse. Muscle atrophy is commonly known to be associated with increased production of reactive oxygen species. However, the role of NRF2, a master regulator of antioxidative response, in skeletal muscle plasticity during microgravity-induced atrophy, is not known. To investigate the role of NRF2 in skeletal muscle within a microgravity environment, wild-type and Nrf2-knockout (KO) mice were housed in the International Space Station for 31 days. Gene expression and histological analyses demonstrated that, under microgravity conditions, the transition of type I (oxidative) muscle fibres to type IIa (glycolytic) was accelerated in Nrf2-KO mice without affecting skeletal muscle mass. Therefore, our results suggest that NRF2 affects myofibre type transition during space flight.
Highlights
Microgravity induces skeletal muscle atrophy, in the soleus muscle, which is predominantly composed of slow-twitch myofibre and is sensitive to disuse
We investigated the role of NRF2 in skeletal muscle during microgravity-induced atrophy in space
Since soleus muscles are predominantly composed of slow-type fibres, they contain a significantly higher level of NRF2 protein as well as other oxidative stress-related molecules, such as NQO1 and SOD compared to white vastus muscles that are primarily composed of fast-type fibres[39]
Summary
Microgravity induces skeletal muscle atrophy, in the soleus muscle, which is predominantly composed of slow-twitch myofibre (type I) and is sensitive to disuse. The molecular mechanisms associated with skeletal muscle atrophy and the myofibre type transition remain unclear, with no effective treatment or prevention having been established. To investigate the direct effect of microgravity on skeletal muscle, the Japan Aerospace Exploration Agency (JAXA) developed the multiple artificial gravity research system ‘MARS’ that can simulate artificial gravity 1 g in space using a centrifuge[20,21,22]. Using this system, we have previously shown that the artificial gravity of 1 g in space is comparable to ground control (GC) regarding skeletal muscle mass[21]. Type I fibre-dominant muscles, such as the soleus muscles, are more sensitive to microgravity than type II fibredominant muscles, resulting in a severe loss of muscle mass and slow-to-fast fibre transition[23]
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