Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle

There is evidence that burn injury stimulates ubiquitin-proteasome-dependen t protein breakdown in skeletal muscle. In this proteolytic pathway, protei n substrates are conjugated to multiple molecules of ubiquitin, whereafter they are recognized, unfolded and degraded by the multicatalytic 26 S prote ase complex. The 20 S proteasome is the catalytic core of the 26 S protease complex. The influence of burn injury on the expression and activity of th e 20 S proteasome has not been reported. We tested the hypothesis that burn injury increases 20 S proteasome activity and the expression of mRNA for t he 20 S proteasome subunits RC3 and RC7. Proteolytic activity of isolated 2 0 S proteasomes, assessed as activity against fluorogenic peptide substrate s, was increased in extensor digitorum longus muscles from burned rats. Nor thern-blot analysis revealed that the expression of mRNA for RC3 and RC7 wa s increased by 100% and 80% respectively following burn injury. Increased a ctivity and expression of the 20 S proteasome in muscles from burned rats s upport the concept that burn-induced muscle cachexia is at least, in part, regulated by the ubiquitin-proteasome proteolytic pathway.