Contribution of the ubiquitin-proteasome pathway to overall muscle proteolysis in hypercatabolic patients

The influence of the gene expression of critical components of the cytoplas mic and lysosomal proteolytic pathways on the rate of protein degradation w as evaluated in the leg skeletal muscle of 8 severely traumatized patients. Muscle proteolysis was determined as the intramuscular phenylalanine rate of appearance by L-[ring-H-2(5)]phenylalanine infusion and the leg arteriov enous catheterization technique combined with muscle biopsy. Muscle mRNA le vels of UbB polyubiquitin and cathepsin B were determined by reverse transc riptase-competitive polymerase chain reaction and expressed as a percent of the mRNA level of the housekeeping gene glyceraldehyde-3-phosphate dehydro genase (GAPDH). In the patients, individual values for UbB polyubiquitin mR NA levels directly correlated with the rate of muscle proteolysis (r = .76, P < .05), whereas no correlation (r = .10) was found between cathepsin B m RNA levels and proteolysis. Thus, after trauma, the rate of muscle proteoly sis appears to be largely regulated by the ubiquitin-proteasome system at t he level of gene transcription. Copyright (C) 2000 by W.B. Saunders Company .