TUMOR-NECROSIS-FACTOR-ALPHA INCREASES THE UBIQUITINIZATION OF RAT SKELETAL-MUSCLE PROTEINS

An acute intravenous administration of 100 mug/kg body weight of recom binant tumour necrosis factor-alpha (TNF) resulted in a time-dependent increase in the levels of both free and conjugated ubiquitin in rat s keletal muscle. The effects of the cytokine were more pronounced in th e 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 importa nt role in the mechanism triggered by TNF which is responsible for enh anced muscle proteolysis in sepsis and other pathological states.