Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy
Open accessAbstract
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.
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The ubiquitin-proteasome system (UPS) represents the major intracellular proteolysis machinery responsible for degradation of major contractile proteins and contributes significantly to muscle atrophy and sarcopenia in both animal and human models.
“Although several proteolytic systems are involved in protein turnover in skeletal muscle, recent studies suggested that the ubiquitin-proteasome system (UPS) represents the major intracellular proteolysis machinery responsible for the degradation of major contractile proteins, and contributes significantly to muscle atrophy and sarcopenia in both animal and human models [22,23].”
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- Authors
- Bialek, P., Morris, C., Parkington, J., St. Andre, M., Owens, J., Yaworsky, P., Seeherman, H., & Jelinsky, S. A.
- Affiliations
- Pfizer (United States) (US)
- Tissue Repair, Pfizer Research, Cambridge, Massachusetts
- Corresponding author
- Jelinsky, Scott A.
- Venue
- Physiological Genomics
- Publisher
- American Physiological Society
- Published
- 2011-10
- Volume
- 43
- Issue
- 19
- Pages
- 1075-1086
- ISSN
- 1094-8341 (ISSN-L)
- 1531-2267
- PMC
- PMC3217324
- OpenAlex
- W2017867760
- Cited by
- 57
- References
- 70
- Citations by year
- 2026: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 1 · 2012: 4
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Genomics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- skeletal muscle atrophy, disuse, tenotomy, ubiquitin-proteasome system, lysosomal degradation, matrix metalloproteinases, autophagy, gastrocnemius, gene expression profiling, muscle fiber size
- MeSH terms
- Achilles Tendon, Animals, Hindlimb, Male, Mice, Inbred C57BL, Muscular Atrophy, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Proteasome Endopeptidase Complex, Mice, Rats, Tenotomy, In Vitro Techniques
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