title: Resistance exercise, but not endurance exercise, induces IKKβ phosphorylation in human skeletal muscle of training-accustomed individuals.
abstract: The mammalian target of rapamycin complex 1 (mTORC1) is considered an important role in the muscular adaptations to exercise. It has been proposed that exercise-induced signaling to mTORC1 do not require classic growth factor PI3K/Akt signaling. Activation of IKKβ and the mitogen-activated protein kinases (MAPKs) Erk1/2 and p38 has been suggested to link inflammation and cellular stress to activation of mTORC1 through the tuberous sclerosis 1 (TSC1)/tuberous sclerosis 2 (TSC2) complex. Consequently, activation of these proteins constitutes potential alternative mechanisms of mTORC1 activation following exercise. Previously, we demonstrated that mTOR is preferentially activated in response to resistance exercise compared to endurance exercise in trained individuals without concomitant activation of Akt. In the present study, we extended this investigation by examining IκB kinase complex (IKK), TSC1, MAPK, and upstream Akt activators, along with gene expression of selected cytokines, in skeletal muscles from these subjects. Biopsies were sampled prior to, immediately after, and in the recovery period following resistance exercise, endurance exercise, and control interventions. The major finding was that IKKβ phosphorylation increased exclusively after resistance exercise. No changes in TSC1, Erk1/2, insulin receptor, or insulin receptor substrate 1 phosphorylation were observed in any of the groups, while p38 phosphorylation was higher in the resistance exercise group compared to both other groups immediately after the intervention. Resistance and endurance exercise increased IL6, IL8, and TNFα gene expression immediately after exercise. The non-exercise control group demonstrated that cytokine gene expression is also sensitive to repeated biopsy sampling, whereas no effect of repeated biopsy sampling on protein expression and phosphorylation was observed. In conclusion, resistance exercise, but not endurance exercise, increases IKKβ phosphorylation in trained human subjects, which support the idea that IKKβ can influence the activation of mTORC1 in human skeletal muscle.
authors.affiliation: Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus, Denmark.
authors.forename: Andreas Buch
authors.initials: AB
authors.lastname: Møller
authors.forename: Mikkel Holm
authors.initials: MH
authors.lastname: Vendelbo
authors.forename: Stine Klejs
authors.initials: SK
authors.lastname: Rahbek
authors.forename: Berthil Forrest
authors.initials: BF
authors.lastname: Clasen
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Kristian
authors.initials: K
authors.lastname: Vissing
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
mesh_terms: D015444:Exercise / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D010807:Physical Endurance / Q000502:physiology*; D055070:Resistance Training; D058570:TOR Serine-Threonine Kinases; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases