title: Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle.
abstract: OBJECTIVE
  Production of reactive oxygen species (ROS) in skeletal muscle is markedly increased during exercise and may be essential for exercise adaptation. We, therefore, investigated the effects of infusion with the antioxidant N-acetylcysteine (NAC) on exercise-induced activation of signalling pathways and genes involved in exercise adaptation in human skeletal muscle.
  
  
  METHODS
  Subjects completed two exercise tests, 7 days apart, with saline (control, CON) or NAC infusion before and during exercise. Exercise tests comprised of cycling at 71% VO(2peak) for 45 min, and then 92% VO(2peak) to fatigue, with vastus lateralis biopsies at pre-infusion, after 45-min cycling and at fatigue.
  
  
  RESULTS
  Analysis was conducted on the mitogen-activated protein kinase signalling pathways, demonstrating that NAC infusion blocked the exercise-induced increase in JNK phosphorylation, but not ERK1/2, or p38 MAPK. Nuclear factor-κB p65 phosphorylation was unaffected by exercise; however, it was reduced in NAC at fatigue by 14% (P < 0.05) compared with pre-infusion. Analysis of exercise and/or ROS-sensitive genes demonstrated that exercise-induced mRNA expression is ROS dependent of MnSOD, but not PGC-1α, interleukin-6, monocyte chemotactic protein-1, or heat-shock protein 70.
  
  
  CONCLUSIONS
  These results suggest that inhibition of ROS attenuates some skeletal muscle cell signalling pathways and gene expression involved in adaptations to exercise.
authors.affiliation: School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Vic., Australia. aaron.petersen@vu.edu.au
authors.forename: A C
authors.initials: AC
authors.lastname: Petersen
authors.forename: M J
authors.initials: MJ
authors.lastname: McKenna
authors.forename: I
authors.initials: I
authors.lastname: Medved
authors.forename: K T
authors.initials: KT
authors.lastname: Murphy
authors.forename: M J
authors.initials: MJ
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Della Gatta
authors.forename: D
authors.initials: D
authors.lastname: Cameron-Smith
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000222:Adaptation, Physiological; D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000008:administration & dosage*; D001642:Bicycling; D001706:Biopsy; D018932:Chemokine CCL2 / Q000235:genetics; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D018763:Muscle Fatigue; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014739:Victoria; D055815:Young Adult
chemical_list: D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D020672:I-kappa B Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D013482:Superoxide Dismutase; D048031:JNK Mitogen-Activated Protein Kinases; D000111:Acetylcysteine