Cachexia is often associated with severe loss of skeletal muscle mass and a reduced energy metabolism. The maintenance of muscle mass can be generally regarded as a simple balance between protein synthesis and protein degradation. Several evidences are available in the current literature favoring a model in which myofilaments are released from the sarcomere by the action of calciumactivated calpains followed by the degradation of the myofilaments by the ubiquitin proteasome system. The initiation of the protein breakdown machinery is regulated by several factors like inflammatory cytokines, angiotensin II, insulin / insulin like growth factor 1 and reactive oxygen species. These factors also have the capability to influence PGC-1alpha activity, thereby regulating mitochondrial energy production. All these molecular alterations regulating muscle mass and energy production in the skeletal muscle finally leads to a reduction in exercise capacity in cachexia.
Keywords: Ubiquitin-proteasome-system (UPS), muscle protein balance, exercise training, cachexia, mitochondria, inflammatory cytokines, reactive oxygen species, atrophy, insulin, myostatin
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