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J Appl Physiol (June 5, 2008). doi:10.1152/japplphysiol.90558.2008
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Submitted on April 23, 2008
Revised on May 27, 2008
Accepted on June 2, 2008

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

Per A Tesch1*, Ferdinand von Walden2, Thomas Gustafsson2, Richard M Linnehan3, and Todd A. Trappe4

1 Mid Sweden University
2 Karolinska Institutet
3 NASA
4 Ball State University

* To whom correspondence should be addressed. E-mail: Per.Tesch{at}miun.se.

Skeletal muscle atrophy, evident after muscle disuse, unloading or spaceflight, results from decreased protein content as a consequence of either decreased protein synthesis, increased protein breakdown or both. At this time there is 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 hr 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 upon completion of this intervention. The 3MH concentration following 72 hr ULLS (2.01±0.22 nmol/mL) was 44% higher (p<0.05) than before ULLS (1.56±0.20 nmol/mL). The current experimental model and the employed method determining 3MH in microdialysates presents 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 hr 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.




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