Differential Cysteine Labeling
and Global Label-Free
Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging
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Abstract
The
molecular mechanisms underlying skeletal muscle aging and associated
sarcopenia have been linked to an altered oxidative status of redox-sensitive
proteins. Reactive oxygen and reactive nitrogen species (ROS/RNS)
generated by contracting skeletal muscle are necessary for optimal
protein function, signaling, and adaptation. To investigate the redox
proteome of aging gastrocnemius muscles from adult and old male mice,
we developed a label-free quantitative proteomic approach that includes
a differential cysteine labeling step. The approach allows simultaneous
identification of up- and downregulated proteins between samples in
addition to the identification and relative quantification of the
reversible oxidation state of susceptible redox cysteine residues.
Results from muscles of adult and old mice indicate significant changes
in the content of chaperone, glucose metabolism, and cytoskeletal
regulatory proteins, including Protein DJ-1, cAMP-dependent protein
kinase type II, 78 kDa glucose regulated protein, and a reduction
in the number of redox-responsive proteins identified in muscle of
old mice. Results demonstrate skeletal muscle aging causes a reduction
in redox-sensitive proteins involved in the generation of precursor
metabolites and energy metabolism, indicating a loss in the flexibility
of the redox energy response. Data is available via ProteomeXchange
with identifier PXD001054