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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.
AuthorsPeter Bialek, Carl Morris, Jascha Parkington, Michael St Andre, Jane Owens, Paul Yaworsky, Howard Seeherman, Scott A Jelinsky
JournalPhysiological genomics (Physiol Genomics) Vol. 43 Issue 19 Pg. 1075-86 (Oct 06 2011) ISSN: 1531-2267 [Electronic] United States
PMID21791639 (Publication Type: Journal Article)
Chemical References
  • Proteasome Endopeptidase Complex
Topics
  • Achilles Tendon (injuries, metabolism)
  • Animals
  • Gene Expression Profiling
  • Hindlimb (injuries, metabolism)
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal (injuries, metabolism, pathology)
  • Muscular Atrophy (metabolism, pathology)
  • Proteasome Endopeptidase Complex (metabolism)
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tenotomy

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