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J Proteome Res. 2014 Nov 7;13(11):5008-21. doi: 10.1021/pr5006394. Epub 2014 Sep 16.

Differential cysteine labeling and global label-free proteomics reveals an altered metabolic state in skeletal muscle aging.

Author information

1
MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Aging (CIMA), Skeletal Muscle Pathophysiology Research Group, Institute of Ageing and Chronic Disease, ‡Protein Function Group, Institute of Integrative Biology, University of Liverpool , Liverpool L69 3GA, United Kingdom.

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.

KEYWORDS:

Grp78; Redox proteomics; aconitase and sirtuin1; aging; skeletal muscle metabolism

PMID:
25181601
PMCID:
PMC4227305
DOI:
10.1021/pr5006394
[Indexed for MEDLINE]
Free PMC Article

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