We evaluated the effects of proteasome inhibitors - a peptide aldehyde MG132, and two vinylsulfone inhibitors ZL3VS and AdaAhx3L3VS - on protein metabolism in sepsis. Sepsis was induced in rats by caecal ligation and puncture.
Parameters of protein metabolism were measured in incubated rat skeletal muscles. Total proteolysis was determined according to the rates of tyrosine release into the medium during incubation.
The ratesof protein synthesis and leucine oxidation were evaluated by incubating muslces in medium containing L-/1-14C/leucine. In the septic muscles, all three inhibitors testedhad no effect on protein synthesis.MG132 decreased proteolysis by more then 50%, AdaAhx3L3VS by 20%, while the effect of ZL3VS was not significant.
We conclude, that MG132 and AdaAhx3L3VS reversed at least partly the protein catabolism in sepsis, as they decreased the proteolysis and did not change the protein synthesis.