Prolonged periods of skeletal muscle inactivity due to
bed rest,
denervation, hindlimb unloading, immobilization, or microgravity can result in significant
muscle atrophy. The
muscle atrophy is characterized as decreased muscle fiber cross-sectional area and
protein content, reduced force, increased
insulin resistance as well as a slow to fast fiber type transition. The decreases in
protein synthesis and increases in protein degradation rates account for the majority of the rapid loss of
muscle protein due to disuse. However, we are just beginning to pay more attention on the identification of genes involved in triggering initial responses to physical inactivity/microgravity. Our review mainly focuses on the signaling pathways involved in
protein loss during
disuse atrophy, including two recently identified
ubiquitin ligases: muscle RING finger 1 (MuRF1) and
muscle atrophy F-box (MAFbx). Recent reports suggest that inhibition of the IGF-1/PI3K/Akt pathway in muscle may be involved in the progression of
disuse atrophy.
NF-kappaB seems to be a key intracellular signal transducer in
disuse atrophy. Factors such as
myostatin, p38 and
calcineurin can induce
muscle protein loss under specified conditions, but further experiments are needed to determine whether they are necessary components of
disuse atrophy. Where possible, the molecular mechanisms underlying the slow to fast fiber type transition and increased
insulin resistance in atrophic muscles are discussed as well. Collectively, the disuse-induced
muscle atrophy is a highly ordered process that is controlled by interactions between intracellular signaling pathways rather than isolated pathways.