Muscle-type dependent sarcolemmal NOS1 mislocalization following 91 days exposure to effective microgravity onboard the International Space Station (ISS).

Exposure to eective microgravity (G) causes numerous adaptive changes to skeletal muscle, which usually lead to a pronounced muscle atrophy. This evidence was obtained in animal experiments in short-term space ight missions. However, the eects of long-term exposure to eective G is still unexplored. This contribution presents the analysis of nitric oxide synthase-1 (NOS1) gene expression and subcellular distribution carried out in soleus (SOL) and extensor digitorum longus (EDL) of mice housed for 91 days in a mice drawer system (MDS) onboard the ISS (1). The long-term exposure to G onboard the ISS caused a signicant muscle atrophy to anti-gravity soleus but not to the fast-twitch EDL. Atrophy was associated to the altered expression of diverse genes (1). The present results show that NOS1 expression was highly misregulated in both soleus and EDL of space own mice. Moreover, laser confocal microscope image analysis demonstrates that space ight induced translocation of sarcolemmal NOS1 into the cytosol in soleus but not in EDL. This is in agreement with the sarcolemma-to-cytosol NOS1 mislocalization observed in ground-based microgravity models (2,3). Our results strongly support the hypothesis that preservation of NOS/NO signaling in EDL muscle might represent an adaptive protective process that explains the absence of atrophy even after the prolonged exposure to long-term exposure to microgravity. The MDS project was sponsored by the Italian Space Agency. (1) Sandona et al., PlosOne 2012 in press); (2) Suzuki N, et al. (2007) J Clin Invest 117: 2468-2476; (3) Rudnick J, et al. (2004) FASEB J 18: 1228-1230. Sponsor: DLR 50WB1121