title: Rapamycin does not prevent increases in myofibrillar or mitochondrial protein synthesis following endurance exercise.
abstract: The present study aimed to investigate the role of the mechanistic target of rapamycin complex 1 (mTORC1) in the regulation of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis following endurance exercise. Forty-two female C57BL/6 mice performed 1 h of treadmill running (18 m min(-1) ; 5° grade), 1 h after i.p. administration of rapamycin (1.5 mg · kg(-1) ) or vehicle. To quantify skeletal muscle protein fractional synthesis rates, a flooding dose (50 mg · kg(-1) ) of l-[ring-(13) C6 ]phenylalanine was administered via i.p. injection. Blood and gastrocnemius muscle were collected in non-exercised control mice, as well as at 0.5, 3 and 6 h after completing exercise (n = 4 per time point). Skeletal muscle MyoPS and MitoPS were determined by measuring isotope incorporation in their respective protein pools. Activation of the mTORC1-signalling cascade was measured via direct kinase activity assay and immunoblotting, whereas genes related to mitochondrial biogenesis were measured via a quantitative RT-PCR. MyoPS increased rapidly in the vehicle group post-exercise and remained elevated for 6 h, whereas this response was transiently blunted (30 min post-exercise) by rapamycin. By contrast, MitoPS was unaffected by rapamycin, and was increased over the entire post-exercise recovery period in both groups (P < 0.05). Despite rapid increases in both MyoPS and MitoPS, mTORC1 activation was suppressed in both groups post-exercise for the entire 6 h recovery period. Peroxisome proliferator activated receptor-γ coactivator-1α, pyruvate dehydrogenase kinase 4 and mitochondrial transcription factor A mRNA increased post-exercise (P < 0.05) and this response was augmented by rapamycin (P < 0.05). Collectively, these data suggest that endurance exercise stimulates MyoPS and MitoPS in skeletal muscle independently of mTORC1 activation.
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.|Neurobiology, Physiology and Behaviour, University of California, Davis, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Philp
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Sciences Graduate Program, University of California, San Diego, CA, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Schenk
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Perez-Schindler
authors.affiliation: School of Sport, University of Stirling, Stirling, UK.
authors.forename: D Lee
authors.initials: DL
authors.lastname: Hamilton
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.|Department of Kinesiology, McMaster University, Hamilton, ON, CA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Breen
authors.affiliation: Neurobiology, Physiology and Behaviour, University of California, Davis, CA, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Laverone
authors.affiliation: School of Sport, University of Stirling, Stirling, UK.
authors.forename: Stewart
authors.initials: S
authors.lastname: Jeromson
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, ON, CA.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Phillips
authors.affiliation: Neurobiology, Physiology and Behaviour, University of California, Davis, CA, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
mesh_terms: D000818:Animals; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001678:Organelle Biogenesis; D010805:Physical Conditioning, Animal / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus