Ubiquitin gene expression in skeletal muscle is increased during sepsis: involvement of TNF-alpha but not IL-1.

Septic rats showed an enhanced expression in skeletal muscle of both 1.2 (500%) and 2.4 (530%) kb mRNAs for the peptide ubiquitin, which reflects the activity of the ATP-ubiquitin-dependent proteolytic system. An acute intravenous administration of 100 micrograms/kg body weight of human recombinant tumour necrosis factor-alpha (TNF) also resulted in an important increase in the levels of ubiquitin mRNAs in rat skeletal muscle, while administration of a similar amount of human recombinant interleukin-1-beta did not. The results presented here, together with previous observations demonstrating that TNF increases the conjugation of proteins with ubiquitin in rat skeletal muscle (1), 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.