Mechanical loading modulates AMPK and mTOR signaling in muscle cellsShow others and affiliations
2024 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 23, no 10, p. 4286-4295Article in journal (Refereed) Published
Abstract [en]
Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance the metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, which is influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interaction with the mTOR signaling pathway. Proteomic analysis of muscle cells subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensities of 5% and 2% as well as the control. Additionally, 10% SL suppressed RNA and protein synthesis while activating AMPK and inhibiting the mTOR pathway. We also found that SRSF2, necessary for pre-mRNA splicing, is regulated by AMPK and mTOR signaling, which, in turn, is regulated in an intensity-dependent manner by SL with the highest expression in 2% SL. Further examination showed that the ADP/ATP ratio was increased after 10% SL compared to the control and that SL induced changes in mitochondrial biogenesis. Furthermore, Seahorse assay results indicate that 10% SL enhances mitochondrial respiration. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in muscle cells.
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2024. Vol. 23, no 10, p. 4286-4295
Keywords [en]
ADP/ATP ratio, AMPK, exercise adaptation, mechanical loading, mitochondrial biogenesis, mTOR, protein synthesis, proteomics analysis, RNA sequencing, skeletal muscle
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-229419DOI: 10.1021/acs.jproteome.4c00242ISI: 001302852000001PubMedID: 39213513Scopus ID: 2-s2.0-85202738975OAI: oai:DiVA.org:umu-229419DiVA, id: diva2:1896120
Funder
Åke Wiberg Foundation, M20-0236Åke Wiberg Foundation, M22-0008Swedish Research Council, P2022-0010Swedish Research Council, P2023-0011Swedish Research Council, P2024-0001The Kempe Foundations, JCK-2032.22024-09-092024-09-092024-10-28Bibliographically approved