Shared and unique phosphoproteomics responses in skeletal muscle from exercise models and in hyperammonemic myotubes

• Published in: iScience Vol. 25; no. 11; p. 105325
• Main Authors: Welch, Nicole, Singh, Shashi Shekhar, Musich, Ryan, Mansuri, M. Shahid, Bellar, Annette, Mishra, Saurabh, Chelluboyina, Aruna K., Sekar, Jinendiran, Attaway, Amy H., Li, Ling, Willard, Belinda, Hornberger, Troy A., Dasarathy, Srinivasan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-11-2022; Elsevier
• Subjects: Biological sciences; Cell biology; Functional aspects of cell biology; Omics; Proteomics; Cell biology; Biological sciences; Functional aspects of cell biology; Omics; Proteomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105325

Skeletal muscle generation of ammonia, an endogenous cytotoxin, is increased during exercise. Perturbations in ammonia metabolism consistently occur in chronic diseases, and may blunt beneficial skeletal muscle molecular responses and protein homeostasis with exercise. Phosphorylation of skeletal muscle proteins mediates cellular signaling responses to hyperammonemia and exercise. Comparative bioinformatics and machine learning-based analyses of published and experimentally derived phosphoproteomics data identified differentially expressed phosphoproteins that were unique and shared between hyperammonemic murine myotubes and skeletal muscle from exercise models. Enriched processes identified in both hyperammonemic myotubes and muscle from exercise models with selected experimental validation included protein kinase A (PKA), calcium signaling, mitogen-activated protein kinase (MAPK) signaling, and protein homeostasis. Our approach of feature extraction from comparative untargeted “omics” data allows for selection of preclinical models that recapitulate specific human exercise responses and potentially optimize functional capacity and skeletal muscle protein homeostasis with exercise in chronic diseases.
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•Hyperammonemia occurs in a number of chronic diseases and physical exercise•Beneficial responses to exercise may be blunted by increased muscle ammoniagenesis•Comparative phosphoproteomics show potential modifiable shared molecular responses•Exercise capacity in chronic disease may be improved by targeting hyperammonemia
Biological sciences; Cell biology; Functional aspects of cell biology; Omics; Proteomics.