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Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice
Published on: November 3, 2013
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Dynamic changes in the mouse skeletal muscle proteome during denervation-induced atrophy
Franziska Lang1, Sriram Aravamudhan2, Hendrik Nolte1
1Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 50931 Cologne, Germany.
Disease Models & Mechanisms
|May 27, 2017
Summary
Denervation causes muscle atrophy by altering protein expression and synthesis. This study reveals new proteins involved in muscle loss and suggests protein stabilization, not just synthesis changes, drives muscle adaptation.
Area of Science:
- Proteomics and Molecular Biology
- Muscle Physiology
- Biochemistry
Background:
- Neuronal stimulation loss leads to muscle atrophy via increased protein breakdown and decreased synthesis.
- Understanding the molecular mechanisms of denervation-induced muscle atrophy is crucial for developing therapeutic strategies.
Purpose of the Study:
- To comprehensively analyze protein expression, synthesis, and ubiquitination changes during denervation-induced muscle atrophy in mice.
- To identify novel proteins and pathways involved in muscle mass regulation.
Main Methods:
- Utilized stable isotope labeling and mass spectrometry to quantify protein expression in denervated mouse gastrocnemius muscle.
- Employed stable isotope labeling of amino acids in cell culture (SILAC) diet and pulse labeling to measure protein synthesis rates.
- Analyzed ubiquitin remnant peptides to identify proteasomal pathway substrates.
Main Results:
- 850 out of 4279 quantified skeletal muscle proteins were significantly differentially expressed within two weeks of denervation.
- Identified 43 proteins with differential lysine incorporation, indicating altered protein synthesis rates.
- Revealed a diglycine signature in metabolic and myofibrillar proteins, including myosin heavy chains, myomesins, and titin, during denervation.
- Identified 92 proteins with atrogene-like regulation not previously linked to denervation-induced atrophy.
Conclusions:
- Denervation-induced muscle atrophy involves complex proteomic alterations, including changes in protein expression, synthesis, and ubiquitination.
- Protein stabilization appears to be a key mechanism for upregulating specific proteins during muscle atrophy.
- This study provides an integrated view of molecular events during muscle atrophy, identifying potential therapeutic targets.
