title: Activation of Akt as a potential mediator of adaptations that reduce muscle injury.
abstract: Contraction-induced injury occurs when a muscle is stretched while activated (lengthening contraction). Exposure to a bout of lengthening contractions results in protection from subsequent lengthening contraction-induced injury as well as an elevation in phosphorylated Akt and p70S6K. Whether Akt or p70S6K is involved in the protection from contraction-induced injury is unclear. To test for a specific role of Akt and/or p70S6K to induce protective adaptations, we used a conditioning protocol of passive stretches that reduces contraction-induced injury with minimal involvement of other cellular responses that have been associated with the Akt signaling pathway, such as increased metabolism, cell growth, and cell death.
  
  
  OBJECTIVE
  To determine whether activation of Akt or p70S6K is necessary to induce protective adaptations.
  
  
  METHODS
  Extensor digitorum longus muscles of anesthetized mice were administered 75 lengthening contractions in situ with or without previous exposure to 75 passive stretches 1 h, 24 h, 3 d, or 14 d prior to lengthening contractions.
  
  
  RESULTS
  Compared with unconditioned muscles, the deficit in isometric force and number of injured fibers 3 d following lengthening contractions were smaller by half for passive-stretch-conditioned muscles from all time points. Phosphorylation of Akt and p70S6K were analyzed by Western blot 0 or 3 h following either lengthening contractions or passive stretches. Whereas lengthening contractions increased phosphorylation of Akt at 0 h and p70S6K at 3 h, passive stretches did not at any time increase phosphorylation of Akt or p70S6K despite reducing contraction-induced injury.
  
  
  CONCLUSIONS
  Activation of neither Akt nor p70S6K is necessary to induce adaptations that reduce the severity of contraction-induced injury.
authors.affiliation: Institute of Gerontology and University of Colorado, Boulder, CO, USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Lockhart
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mazzeo
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D004558:Electric Stimulation; D007537:Isometric Contraction / Q000502:physiology; D049449:Luminescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000502:physiology*; D012038:Regeneration / Q000502:physiology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000032:analysis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa