N-peptidyl-O-carbamoyl amino acid hydroxamates: irreversible inhibitors for the study of the S2'' specificity of cysteine proteinases

An acute intravenous administration of 100 micrograms/kg body weight of recombinant tumour necrosis factor-alpha (TNF) resulted in a time-dependent increase in the levels of both free and conjugated ubiquitin in rat skeletal muscle. The effects of the cytokine were more pronounced in the red muscle soleus than in the white muscle EDL. In the former muscle type, TNF-treatment also resulted in a time-dependent increase in the percentage of free ubiquitin. The results suggest that the ubiquitin system for non-lysosomal protein degradation could have a very important role in the mechanism triggered by TNF which is responsible for enhanced muscle proteolysis in sepsis and other pathological states.