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

• DOI: 10.1053/meta.2000.6236
• Publication Date: 2005-04-13T14:20:55Z
• Authors: Gianni Biolo; Alessandra Bosutti; Fulvio Iscra; Gabriele Toigo; Antonino Gullo; Gianfranco Guarnieri
• Keywords: Adult; Male; 0301 basic medicine; Proteasome Endopeptidase Complex; Transcription, Genetic; Phenylalanine; muscle metabolism; Muscle Proteins; Cathepsin B; 03 medical and health sciences; Biopolymers; Multienzyme Complexes; Ubiquitin-proteasome pathway; hypercatabolic patients.; Humans; RNA, Messenger; Muscle, Skeletal; Polyubiquitin; Ubiquitins; Ubiquitin-proteasome pathway; Dietary energy, Gene transcription, Microarray, Pig, Skeletal muscle; trauma; Dietary energy, Gene transcription, Microarray, Pig, Skeletal muscle; 0303 health sciences; 3. Good health; Cysteine Endopeptidases; trauma; Gene Expression Regulation; Wounds and Injuries; Ubiquitin-proteasome pathway; muscle metabolism; hypercatabolic patients.

The influence of the gene expression of critical components of the cytoplasmic and lysosomal proteolytic pathways on the rate of protein degradation was 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-2H5]phenylalanine infusion and the leg arteriovenous catheterization technique combined with muscle biopsy. Muscle mRNA levels of UbB polyubiquitin and cathepsin B were determined by reverse transcriptase-competitive polymerase chain reaction and expressed as a percent of the mRNA level of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the patients, individual values for UbB polyubiquitin mRNA levels directly correlated with the rate of muscle proteolysis (r = .76, P < .05), whereas no correlation (r = .10) was found between cathepsin B mRNA levels and proteolysis. Thus, after trauma, the rate of muscle proteolysis appears to be largely regulated by the ubiquitin-proteasome system at the level of gene transcription.