Modulation of Murf-1 and MAFbx expression in the myocardium by physical exercise training.
BACKGROUND
Cell culture and animal studies demonstrated the impact of muscle ring finger 1 (Murf-1) and muscle atrophy f-box (MAFbx) expression on muscle atrophy and cardiac remodeling. Exercise training (ET) exhibits great potential to attenuate the development of muscle atrophy and cardiac remodeling. The aim of this study was to investigate the impact of ET on myocardial expression of Murf-1 and MAFbx.


METHODS
Three weeks after left anterior descending artery ligation or sham operation rats were divided either into a 4-week training or an inactive control group. At the end of ET the remote myocardium and the corresponding part in the sham-operated rats were collected. The expression of Murf-1 and MAFbx was evaluated by quantitative real time PCR and western blot. The myocardial concentration of tumor necrosis factor-alpha (TNF-alpha) was quantified by enzyme-linked immunosorbent assay.


RESULTS
Seven weeks after left anterior descending artery ligation (myocardial infarction) the messenger RNA expression of Murf-1 (sham: 1.8+/-0.3 vs. Mi: 5.9+/-1.2 arb. units; P<0.05), MAFbx (sham: 13.9+/-2.4 vs. Mi: 84.0+/-22.7 arb. units; P<0.05) and the local TNF-alpha concentration (sham: 322+/-48 vs. Mi: 1010+/-170 pg/mg; P<0.001) was significantly upregulated in the myocardium. Four weeks of ET led to a significantly lower expression of Murf-1 (1.2+/-0.6 arb. units) MAFbx (6.4+/-2.6 arb. units) and TNF-alpha (419+/-64 pg/mg) when compared with the inactive group. Furthermore, a negative correlation between myocardial function and Murf-1/MAFbx expression was detected.


CONCLUSIONS
The results of these experiments demonstrate that Murf-1/MAFbx expression is upregulated in the myocardium after induction of heart failure. Regular ET has the potential to reduce the expression of these atrophy-related E3 ubiquitin ligases possibly via its anti-inflammatory action.
Department of Cardiology, University of Leipzig, Leipzig Heart Center, Leipzig, Germany. adav@medizin.uni-leipzig.de
Volker
V
Adams
Axel
A
Linke
Stephan
S
Gielen
Sandra
S
Erbs
Rainer
R
Hambrecht
Gerhard
G
Schuler
D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000534:rehabilitation*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000534:rehabilitation; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D009124:Muscle Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D014409:Tumor Necrosis Factor-alpha; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases