Activation of mTOR for the loss of skeletal muscle in a hindlimb-suspended rat model

Abstract

The hindlimb-suspended or unloading rodent model was developed to mimic the microgravity of a spaceflight environment and has been used extensively to study the physiological responses to various aspects of musculoskeletal loading and unloading. This study investigated a compensating response to skeletal muscle loss in a hindlimb-suspended model that involves up-regulation of mTOR phosphorylation at four weeks. Body weight and muscle volume significantly decreased over four weeks in the hindlimb-suspended group compared with the sham control. Expressions of p-mTOR, raptor protein, p-p70S6K, p-Akt, and p-ERK, anti- or pro-apoptotic p53, Bcl-2, Bcl-XL, Bax, and Bak proteins were significantly increased in the hindlimb-suspended group compared to the sham control at four weeks. These results indicate that p-mTOR and p-Akt/p-ERK proteins might be up-regulated to compensate for the loss of skeletal muscle in the hindlimb-suspended model. Expressions of p-AMPK, IRS1, and IRS2 proteins were significantly increased, but that of p-eIF2α was significantly reduced in the hindlimb-suspended group compared to the sham control at four weeks. Our results suggest that the loss of skeletal muscle in a hindlimb-suspended model induces activation of p-mTOR and p-Akt/p-ERK proteins, and that these signaling pathways may preserve protein synthesis and cell growth in skeletal muscles of hindlimb-suspended animals.