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 ref lects the activity of the ATP-ubiquitin-dependent proteolytic system. An acute intravenous administration of 100 mu g/kg body weight of huma n recombinant tumour necrosis factor-alpha (TNF) also resulted in an i mportant increase in the levels of ubiquitin mRNAs in rat skeletal mus cle, while administration of a similar amount of human recombinant int erleukin-1-beta did not. The results presented here, together with pre vious 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 ve ry important role in the mechanism triggered by TNF which is responsib le for enhanced muscle proteolysis in sepsis and other pathological st ates. (C) 1995 Academic Press. Inc.