Alcohol accelerates loss of muscle and impairs recovery of muscle mass resulting from disuse atrophy.

Abstract

BACKGROUND:

Muscle disuse atrophy is observed in patients recovering from trauma and there is an increased risk and severity of injury in patients abusing alcohol (EtOH). However, the interaction of EtOH and disuse on muscle protein balance has not been examined. Therefore, the present study addressed the hypothesis that EtOH accelerates the disuse atrophy and/or impairs the accretion of muscle protein during muscle recovery.

METHODS:

To address this aim, disuse atrophy was induced in rats by 3 days of unilateral hindlimb immobilization (casting), using the contralateral leg as control, with EtOH or saline being orally gavaged twice, each day during this period. In a separate study, EtOH-treated rats received Velcade to inhibit proteasomal degradation. Finally, in the last study, rats had 1 limb casted for 5 days, the cast removed, and EtOH or saline gavaged twice daily during a 5-day recovery period. Muscle protein metabolism was assessed using surrogate markers of protein synthesis [i.e., phosphorylation of 4E-binding protein 1 (BP1) and S6 kinase 1 (S6K1)] and protein degradation (i.e., mRNA content of the ubiquitin E3 ligases atrogin-1 and MuRF1).

RESULTS:

Ethanol alone did not decrease muscle weight in the uncasted muscle. However, the loss of mass of immobilized muscle from EtOH-gavaged rats was 80% greater than in the animals not receiving EtOH. This atrophic response was not associated with a change in Akt, 4E-BP1 or S6K1 phosphorylation among groups. In contrast, immobilization alone increased both atrogin-1 and MuRF1 mRNA, and EtOH further increased their expression in immobilized muscle. The proteasome inhibitor Velcade attenuated atrophy produced by EtOH + disuse. When administered during the recovery period, EtOH prevented the normal accretion of muscle mass. This EtOH effect was associated with increased atrogin-1 mRNA, a reduction in 4E-BP1 and S6 phosphorylation, and an increased AMP-activated kinase phosphorylation.

CONCLUSIONS:

Based on the changes in these surrogate markers, our data suggest that EtOH accelerates disuse atrophy by stimulating ubiquitin-mediated proteolysis, and blunts repletion of muscle protein during recovery from disuse by increasing proteolysis and decreasing protein synthesis.

• Authors: Roberto Vargas, Charles H Lang
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 32 Issue 1 Pg. 128-37 (Jan 2008) ISSN: 1530-0277 [Electronic] England
• PMID: 18028527 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Carrier Proteins
• Central Nervous System Depressants
• Eif4ebp1 protein, rat
• Intracellular Signaling Peptides and Proteins
• Muscle Proteins
• Phosphoproteins
• Tripartite Motif Proteins
• Ethanol
• Fbxo32 protein, rat
• SKP Cullin F-Box Protein Ligases
• Trim63 protein, rat
• Ubiquitin-Protein Ligases
• Ribosomal Protein S6 Kinases
• Rps6kb1 protein, rat

Topics

• Animals
• Biomarkers (metabolism)
• Carrier Proteins (metabolism)
• Central Nervous System Depressants (adverse effects)
• Ethanol (adverse effects)
• Immobilization (adverse effects)
• Intracellular Signaling Peptides and Proteins
• Male
• Muscle Proteins (metabolism)
• Muscular Disorders, Atrophic (metabolism)
• Phosphoproteins (metabolism)
• Protein Biosynthesis (physiology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (physiology)
• Ribosomal Protein S6 Kinases (metabolism)
• SKP Cullin F-Box Protein Ligases (metabolism)
• Tripartite Motif Proteins
• Ubiquitin-Protein Ligases (metabolism)