Changes in REDD1, REDD2, and atrogene mRNA expression are prevented in skeletal muscle fixed in a stretched position during hindlimb immobilization.

Immobilized skeletal muscle fixed in a shortened position displays disuse atrophy, whereas when fixed in a stretched position it does not (Goldspink, D. F. (1977) J Physiol 264, 267-282). Although significant advances have been made in our understanding of mechanisms involved in development of atrophy in muscle fixed in a shortened position, little is known about why mass is maintained when muscle is immobilized in a stretched position. In the present study, we hypothesized that skeletal muscle immobilized in a stretched position would be protected from gene expression changes known to be associated with disuse atrophy. To test the hypothesis, male Sprague-Dawley rats were anesthetized using isoflurane and subjected to unilateral hindlimb immobilization for 3 days with the soleus fixed in either a shortened or stretched position. All comparisons were made to the contralateral nonimmobilized muscle. Soleus immobilized in a shortened position exhibited disuse atrophy, attenuated rates of protein synthesis, attenuated mTORC1 signaling, and induced expression of genes for REDD1, REDD2, MAFbx, and MuRF1. In contrast, immobilization of the soleus in a stretched position prevented these changes as it exhibited no difference in muscle mass, rates of protein synthesis, mTORC1 signaling, or expression of genes encoding REDD1, MAFbx or MuRF1, with REDD2 expression being reduced compared to control. In conclusion, fixed muscle length plays a major role in immobilization-induced skeletal muscle atrophy whereby placing muscle in a shortened position leads to induction of gene expression for REDD1, REDD2, and atrogenes.