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Skeletal Muscle Immobilized in a Stretched Position does not Display Characteristics of Disuse Atrophy.

Abstract

Kelleher, A., Gordon, B., Kimball, S., Jefferson, L. The Pennsylvania State University College of Medicine, Hershey, PA.

Purpose: Immobilized skeletal muscle placed in a shortened position displays disuse atrophy, whereas when placed in a stretched position it does not. We hypothesized that characteristics of disuse atrophy such as attenuated rates of protein synthesis and induction of the repressors of mechanistic target of rapamycin complex 1 (mTORC1) signaling, regulated in development and DNA-damage response (REDD)1 and REDD2, and atrogenes, Muscle Atrophy F-box (MAFbx) and Muscle Ring Finger 1 (MuRF1), would not manifest in skeletal muscle immobilized in a stretched position. Methods: Twenty male Sprague-Dawley rats were subjected to unilateral hindlimb immobilization for 3 days. Ten were immobilized in plantarflexion with the soleus muscle placed in a shortened position, while another ten were immobilized in dorsiflexion, with the soleus muscle placed in a stretched position. Soleus muscles from immobilized hindlimbs were compared to contralateral non-immobilized hindlimbs. Results: Soleus muscles immobilized in a shortened position exhibited disuse atrophy, an attenuated rate of protein synthesis (30% of the non-immobilized limb), repressed mTORC1 signaling as assessed by phosphorylation of p70 ribosomal protein S6 kinase 1 (p70S6K1) on Thr389 (15% of the non-immobilized limb), and induction of REDD1, REDD2, MAFbx and MuRF1 gene expression (350%, 600%, 250%, and 200% of the non-immobilized limb, respectively). Soleus muscles immobilized in a stretched position exhibited no differences between immobilized and non-immobilized muscles for muscle mass, rate of protein synthesis, p70S6K1 phosphorylation, or induction of REDD1, REDD2, MAFbx or MuRF1. In addition, soleus muscles immobilized in a stretched position exhibited elevated Akt Ser473 and Forkhead box O3a (FoxO3a) Ser253 phosphorylation, which suggests that FoxO3a-mediated induction of atrogenes is inhibited by Akt signaling. Conclusion: Skeletal muscle immobilized in a stretched position is protected from changes associated with disuse atrophy.

Research funded by NIH DK-15658.

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