Mechanisms accelerating muscle atrophy in catabolic diseases.

In summary, muscle protein loss in uremia is related to activation of the ubiquitin-proteasome proteolytic system to degrade muscle proteins. This response invariably includes increased transcription of genes encoding components of this pathway, suggesting that these illnesses stimulate a program of catabolism. Signals that could activate muscle protein degradation by this system in CRF include metabolic acidosis, impaired response to insulin and high circulating levels of cytokines. The activation mechanism also involves glucocorticoids which are necessary but not sufficient to activate protein degradation in muscle.