Skeletal muscle Rac1 mediates exercise training adaptations towards muscle glycogen resynthesis and protein synthesis

Vista sencilla de ítem
dc.contributor.authorRaun, Steffen H.
dc.contributor.authorHenriquez-Olguín, Carlos
dc.contributor.authorFrank, Emma
dc.contributor.authorSchlabs, Farina
dc.contributor.authorHahn, Nanna Just
dc.contributor.authorRoland Knudsen, Jonas
dc.contributor.authorAli, Mona S.
dc.contributor.authorAndersen, Nicoline R.
dc.contributor.authorMøller, Lisbeth L.V.
dc.contributor.authorDavey, Jonathan
dc.contributor.authorQian, Hongwei
dc.contributor.authorCoelho, Ana
dc.contributor.authorCarl, Christian S.
dc.contributor.authorVoldstedlund, Christian T.
dc.contributor.authorKiens, Bente
dc.contributor.authorHolmdahl, Rikard
dc.contributor.authorGregorevic, Paul
dc.contributor.authorJensen, Thomas E.
dc.contributor.authorDeshmukh, Atul S.
dc.contributor.authorRichter, Erik A.
dc.contributor.authorSylow, Lykke
dc.coverage.spatialNetherlands
dc.date.accessioned2025-12-05T15:53:16Z
dc.date.available2025-12-05T15:53:16Z
dc.date.issued2025-08-28
dc.description.abstractLong-term exercise training elicits tremendous health benefits; however, the molecular understanding is incomplete and identifying therapeutic targets has been challenging. Rho GTPases are among the most regulated groups of proteins after exercise in human skeletal muscle, yet, unexplored candidates for mediating the effects of exercise training. We found that the Rho GTPase Rac1 was activated acutely after multiple exercise modalities in human skeletal muscle. Loss of Rac1 specifically in muscle attenuated contraction-induced muscle protein synthesis, diminished improvements in running capacity, and prevented muscle hypertrophy after exercise training in mice. Additionally, Ncf1* mice revealed that Rac1 regulated glycogen resynthesis via a NOX2-dependent mechanism. Molecularly, Rac1 was required for contraction-induced p38MAPK signaling towards HSP27, MNK1, and CREB phosphorylation. In vivo muscle-targeted overexpression of a hyperactive Rac1-mutant elevated reactive oxidant species production during exercise but did not affect muscle mass. Using mass spectrometry-based proteomics, we found that loss or gain of Rac1 muscle protein affected pathways related to cytoskeleton organization, muscle adaptation, and large ribosomal subunits. Thus, skeletal muscle Rac1 mediates both molecular and functional adaptation to exercise training.
dc.identifier.citationRedox Biology, Vol. 86 (2025) p. 1-14
dc.identifier.doihttps://doi.org/10.1016/j.redox.2025.103844
dc.identifier.issne2213-2317
dc.identifier.orcidhttps://orcid.org/0000-0002-9315-9365
dc.identifier.urihttps://hdl.handle.net/20.500.12254/7393
dc.language.isoen
dc.publisherElsevier
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectRac1
dc.subjectSkeletal muscle
dc.subjectExercise training
dc.subjectContraction
dc.subjectMuscle hypertrophy
dc.subjectMetabolism
dc.subjectGlycogen
dc.subjectProtein synthesis
dc.titleSkeletal muscle Rac1 mediates exercise training adaptations towards muscle glycogen resynthesis and protein synthesis
dc.typeArticle
Archivos
Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
2025 Skeletal muscle Rac1 mediates exercise training adaptations towards muscle glycogen resynthesis and protein synthesis.pdf
Tamaño:
6.78 MB
Formato:
Adobe Portable Document Format
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
347 B
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar
Colecciones
Artículos de Revistas