Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet

Can J Physiol Pharmacol. 2014 Jun;92(6):445-54. doi: 10.1139/cjpp-2013-0290. Epub 2014 Apr 4.

Abstract

The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

Keywords: activité de la caspase-3; caspase-3 activity; diète hypoprotéique hyperglucidique; high-carbohydrate diet; insulin sensitivity; low-protein; overall proteolysis; protein synthesis; protéolyse globale; sensibilité à l’insuline; synthèse protéique; système ubiquitine–protéasome; ubiquitin–proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood
  • Animals
  • Caspase 3 / metabolism*
  • Cathepsin B / metabolism
  • Diet, Protein-Restricted*
  • Dietary Carbohydrates / pharmacology*
  • Dietary Proteins / administration & dosage
  • Dietary Proteins / pharmacology
  • Insulin Resistance
  • Male
  • Muscle Proteins / biosynthesis
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Biosynthesis / drug effects*
  • Proteolysis / drug effects*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Receptor, Insulin / metabolism
  • SKP Cullin F-Box Protein Ligases / biosynthesis
  • Tripartite Motif Proteins
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / biosynthesis

Substances

  • Amino Acids
  • Dietary Carbohydrates
  • Dietary Proteins
  • Muscle Proteins
  • Tripartite Motif Proteins
  • Ubiquitin
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases
  • Receptor, Insulin
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • Cathepsin B
  • Proteasome Endopeptidase Complex