title: Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy.
abstract: Skeletal muscle atrophy can be a consequence of many diseases, environmental insults, inactivity, age, and injury. Atrophy is characterized by active degradation, removal of contractile proteins, and a reduction in muscle fiber size. Animal models have been extensively used to identify pathways that lead to atrophic conditions. We used genome-wide expression profiling analyses and quantitative PCR to identify the molecular changes that occur in two clinically relevant mouse models of muscle atrophy: hindlimb casting and Achilles tendon laceration (tenotomy). Gastrocnemius muscle samples were collected 2, 7, and 14 days after casting or injury. The total amount of muscle loss, as measured by wet weight and muscle fiber size, was equivalent between models on day 14, although tenotomy resulted in a more rapid induction of muscle atrophy. Furthermore, tenotomy resulted in the regulation of significantly more mRNA transcripts then did casting. Analysis of the regulated genes and pathways suggest that the mechanisms of atrophy are distinct between these models. The degradation following casting was ubiquitin-proteasome mediated, while degradation following tenotomy was lysosomal and matrix-metalloproteinase mediated, suggesting a possible role for autophagy. These data suggest that there are multiple mechanisms leading to muscle atrophy and that specific therapeutic agents may be necessary to combat atrophy resulting from different conditions.
authors.affiliation: Tissue Repair, Pfizer Research, Cambridge, Massachusetts 02140, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Bialek
authors.forename: Carl
authors.initials: C
authors.lastname: Morris
authors.forename: Jascha
authors.initials: J
authors.lastname: Parkington
authors.forename: Michael
authors.initials: M
authors.lastname: St Andre
authors.forename: Jane
authors.initials: J
authors.lastname: Owens
authors.forename: Paul
authors.initials: P
authors.lastname: Yaworsky
authors.forename: Howard
authors.initials: H
authors.lastname: Seeherman
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jelinsky
mesh_terms: D000125:Achilles Tendon / Q000293:injuries / Q000378:metabolism; D000818:Animals; D020869:Gene Expression Profiling; D006614:Hindlimb / Q000293:injuries / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058971:Tenotomy
chemical_list: D046988:Proteasome Endopeptidase Complex