The ubiquitin-proteasome and the mitochondria-associated apoptotic pathways are sequentially downregulated during recovery after immobilization-induced muscle atrophy

摘要

Muscle protein loss results from an imbalance between protein synthesis and breakdown rates but also from an imbalance between apoptotic and differentiation-regeneration processes. The ubiquitin (Ub)-proteasome pathway is systematically activated when muscle atrophies extensively and is involved in the breakdown of the major contractile proteins. Basically, there are two main steps in the pathway: 1) covalent attachment of a polyUb degradation signal to the substrate and 2) specific recognition of the polyUb chain and subsequent breakdown of the targeted proteins by the 26S proteasome (2). We and others have previously shown that hindlimb suspension induces atrophy and loss of protein of the rat soleus muscle as a result of an activation of the Ub-proteasome proteolytic pathway (5, 17, 39). Similar observations were reported in muscles of rats exposed to spaceflight or denerva-tion (20, 40)