Direct Effects of
Proteasome Inhibitor AdaAhx3L3VS on Protein and Amino Acid
Metabolism in Rat Skeletal Muscle
J. KADLČÍKOVÁ, M. HOLEČEK1, R.
ŠAFRÁNEK1, I. TILŠER
Department of Pharmacology, Faculty of Pharmacy and 1Department
of Physiology, Faculty of Medicine, Charles University, Hradec
Králové, Czech Republic
Received June 17, 2004
Accepted October 11, 2004
On-line available January 10, 2005
Summary
Proteasome inhibitors are novel potential drugs for therapy of
many diseases, and their effects are not fully understood. We
investigated direct effects of peptide vinylsulfone inhibitor
AdaAhx3L3VS on protein and amino acids metabolism in rat
skeletal muscle. Soleus and extensor digitorum longus muscles
were incubated in a medium containing 30 μmol/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. AdaAhx3L3VS decreased tyrosine release into the medium by
21 and 19 %, decreased leucine
incorporation into proteins by 22 and 12 %, and increased
leucine oxidation by 24 and 19 % in
soleus and extensor digitorum longus muscles, respectively. The
release of amino acids into the medium was reduced. We conclude
that AdaAhx3L3VS significantly decreased proteolysis and protein
synthesis and increased leucine oxidation.
Key words
Proteasome inhibitor • Peptide vinylsulfone • Protein metabolism
• Amino acids
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