Global phosphoproteomic profiling of skeletal muscle in ovarian hormonedeficient mice

Mina P. Peyton, Tzu-Yi Yang, Leeann Higgins, Todd W Markowski, Cha Vue, Laurie L. Parker, Dawn A. Lowe

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Protein phosphorylation is important in skeletal muscle development, growth, regeneration, and contractile function. Alterations in the skeletal muscle phosphoproteome due to aging have been reported in males; however, studies in females are lacking. We have demonstrated that estrogen deficiency decreases muscle force, which correlates with decreased myosin regulatory light chain phosphorylation. Thus, we questioned whether the decline of estrogen in females that occurs with aging might alter the skeletal muscle phosphoproteome. C57BL/6J female mice (6 mo) were randomly assigned to a sham-operated (Sham) or ovariectomy (Ovx) group to investigate the effects of estrogen deficiency on skeletal muscle protein phosphorylation in a resting, noncontracting condition. After 16 wk of estrogen deficiency, the tibialis anterior muscle was dissected and prepped for label-free nano-liquid chromatography-tandem mass spectrometry phosphoproteomic analysis. We identified 4,780 phosphopeptides in tibialis anterior muscles of ovariectomized (Ovx) and Sham-operated (Sham) control mice. Further analysis revealed 647 differentially regulated phosphopeptides (Benjamini–Hochberg adjusted P value < 0.05 and 1.5-fold change ratio) that corresponded to 130 proteins with 22 proteins differentially phosphorylated (3 unique to Ovx, 2 unique to Sham, 6 upregulated, and 11 downregulated). Differentially phosphorylated proteins associated with the sarcomere, cytoplasm, and metabolic and calcium signaling pathways were identified. Our work provides the first global phosphoproteomic analysis in females and how estrogen deficiency impacts the skeletal muscle phosphoproteome.

Original languageEnglish (US)
Pages (from-to)417-432
Number of pages16
JournalPhysiological genomics
Issue number11
StatePublished - Nov 2022

Bibliographical note

Funding Information:
This work was supported by National Institute on Aging Grant R01 AG031743-13 and National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant T32 AR007612.

Publisher Copyright:
© 2022 the American Physiological Society.


  • AMPK
  • estrogen
  • females
  • ovariectomy
  • YAP

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial, Veterinary
  • Research Support, N.I.H., Extramural


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