title: Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure.
abstract: BACKGROUND
  Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF.
  
  
  RESULTS
  Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7(th) month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels.
  
  
  CONCLUSIONS
  Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Telma F
authors.initials: TF
authors.lastname: Cunha
authors.forename: Aline V N
authors.initials: AV
authors.lastname: Bacurau
authors.forename: Jose B N
authors.initials: JB
authors.lastname: Moreira
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Paixão
authors.forename: Juliane C
authors.initials: JC
authors.lastname: Campos
authors.forename: Julio C B
authors.initials: JC
authors.lastname: Ferreira
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Leal
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Negrão
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005081:Exercise Therapy; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex