Language
English
Publication Date
1-14-2025
Journal
The Journal of Investigation
DOI
10.1172/JCI176942
PMID
39808494
PMCID
PMC11870723
Abstract
Eccentric contraction-induced (ECC-induced) force loss is a hallmark of murine dystrophin-deficient (mdx) skeletal muscle that is used to assess efficacy of potential therapies for Duchenne muscular dystrophy. While virtually all key proteins involved in muscle contraction have been implicated in ECC force loss, a unifying mechanism that orchestrates force loss across such diverse molecular targets has not been identified. We showed that correcting defective hydrogen sulfide (H2S) signaling in mdx muscle prevented ECC force loss. We also showed that the cysteine proteome of skeletal muscle functioned as a redox buffer in WT and mdx muscle during ECCs, but that buffer capacity in mdx muscle was significantly compromised by elevated basal protein oxidation. Finally, chemo-proteomic data suggested that H2S protected several proteins central to muscle contraction against irreversible oxidation through persulfidation-based priming. Our results support a unifying, redox-based mechanism of ECC force loss in mdx muscle.
Keywords
Animals, Hydrogen Sulfide, Muscle Contraction, Mice, Muscle, Skeletal, Dystrophin, Mice, Inbred mdx, Muscular Dystrophy, Duchenne, Oxidation-Reduction, Male, Metabolism, Muscle biology, Neuromuscular disease, Proteomics, Skeletal muscle
Published Open-Access
yes
Recommended Citation
Southern, W Michael; Johnson, Erynn E; Fasbender, Elizabeth K; et al., "Impaired Hydrogen Sulfide Biosynthesis Underlies Eccentric Contraction-Induced Force Loss in Dystrophin-Deficient Skeletal Muscle" (2025). Faculty, Staff and Students Publications. 6596.
https://digitalcommons.library.tmc.edu/baylor_docs/6596
Graphical Abstract