Signaling mechanisms involved in disuse muscle atrophy

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Med Hypotheses. 2007 Mar 19

Signaling mechanisms involved in disuse muscle atrophy.

Zhang P, Chen X, Fan M.

China Astronaut Research and Training Center, 1 Yuanmingyuan West

Road, Beijing 100094, PR China.

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.