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Skeletal muscle proteolysis in response to short-term unloading in humans

¹Department of Physiology and Pharmacology, ²Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; ³Human Performance Laboratory, Ball State University, Muncie, Indiana; ⁴Astronaut Office, National Aeronautics and Space Administration, Johnson Space Center, Houston, Texas; and ⁵Department of Health Science, Mid Sweden University, Östersund, Sweden

Submitted 23 April 2008 ; accepted in final form 2 June 2008

Skeletal muscle atrophy is evident after muscle disuse, unloading, or spaceflight and results from decreased protein content as a consequence of decreased protein synthesis, increased protein breakdown or both. At this time, there are essentially no human data describing proteolysis in skeletal muscle undergoing atrophy on Earth or in space, primarily due to lack of valid and accurate methodology. This particular study aimed at assessing the effects of short-term unloading on the muscle contractile proteolysis rate. Eight men were subjected to 72-h unilateral lower limb suspension (ULLS) and intramuscular interstitial levels of the naturally occurring proteolytic tracer 3-methylhistidine (3MH) were measured by means of microdialysis before and on completion of this intervention. The 3MH concentration following 72-h ULLS (2.01 ± 0.22 nmol/ml) was 44% higher (P < 0.05) than before ULLS (1.56 ± 0.20 nmol/ml). The present experimental model and the employed method determining 3MH in microdialysates present a promising tool for monitoring skeletal muscle proteolysis or metabolism of specific muscles during conditions resulting in atrophy caused by, e.g., disuse and real or simulated microgravity. This study provides evidence that the atrophic processes are evoked rapidly and within 72 h of unloading and suggests that countermeasures should be employed in the early stages of space missions to offset or prevent muscle loss during the period when the rate of muscle atrophy is the highest.

contractile protein breakdown; microdialysis; muscle atrophy; spaceflight simulation; 3-methylhistidine