Direct effects of proteasome inhibitor AdaAhx3L3VS on protein and amino acid metabolism in rat skeletal muscle

Abstract

We investigated direct effects of peptide vinylsulfone inhibitor AdaAhx3L3VS on protein and amino acids metabolism in rat skeletal muscle.M.soleus and m.extensor digitorum longus were incubated in metidum containing 30 umol/l AdaAhx3L3VS or no inhibitors.Total proteolysis was determined according to the rates of tyrosine release into the medium during incubation.The rates of leucine oxidation and protein synthesis were evaluated during incubation in medium containing L-[1-14C]leucine.Amino acid concentrations in the medium were measured using HPLC.Statistical comparisons were performed by paired t-tests.AdaAhx3L3VS decreased both proteolysis (by 20%) and protein synthesis (by 10-20%)and increased leucine oxidation.The release of a number of amino acids into the medium was lowered.We conclude that AdaAhx3L3VS decreased overall protein turnover in the muscle tissue.