title: Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig Exercise Intervention in Chronic Heart Failure and Aging catabolism study.
abstract: BACKGROUND
  Muscle wasting occurs in both chronic heart failure (CHF) and normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system and the lysosomal pathway of intracellular proteolysis in muscle biopsies of CHF patients and healthy controls in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance.
  
  
  RESULTS
  Sixty CHF patients (30 patients aged ≤55 years, mean age 46±5 years; 30 patients aged ≥65 years, mean age 72±5 years) and 60 healthy controls (30 subjects aged ≤55 years, mean age 50±5 years; 30 subjects aged ≥65 years, mean age 72±4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention, vastus lateralis muscle biopsies were obtained. The expressions of cathepsin-L and the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time polymerase chain reaction and confirmed by Western blot. At baseline, MuRF-1 expression was significantly higher in CHF patients versus healthy controls (mRNA: 624±59 versus 401±25 relative units; P=0.007). After 4 weeks of exercise training, MuRF-1 mRNA expression was reduced by -32.8% (P=0.02) in CHF patients aged ≤55 years and by -37.0% (P<0.05) in CHF patients aged ≥65 years.
  
  
  CONCLUSIONS
  MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks ubiquitin-proteasome system activation and does so in both younger and older CHF patients.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00176319.
authors.affiliation: Department of Internal Medicine III, University Hospital, Martin Luther University of Halle/Wittenberg, Ernst-Grube Strasse 40, 06120 Halle, Germany. stephan.gielen@uk-halle.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Marcus
authors.initials: M
authors.lastname: Sandri
authors.forename: Irina
authors.initials: I
authors.lastname: Kozarez
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.forename: Norman
authors.initials: N
authors.lastname: Mangner
authors.forename: Karsten
authors.initials: K
authors.lastname: Lenk
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D001706:Biopsy; D056668:Cathepsin L / Q000378:metabolism; D002908:Chronic Disease; D015444:Exercise / Q000502:physiology*; D005858:Germany / Q000453:epidemiology; D006333:Heart Failure / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010807:Physical Endurance / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D056668:Cathepsin L; D046988:Proteasome Endopeptidase Complex