title: Contribution of the ubiquitin-proteasome pathway to overall muscle proteolysis in hypercatabolic patients.
abstract: 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.
authors.affiliation: Istituto di Clinica Medica, University of Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Biolo
authors.forename: A
authors.initials: A
authors.lastname: Bosutti
authors.forename: F
authors.initials: F
authors.lastname: Iscra
authors.forename: G
authors.initials: G
authors.lastname: Toigo
authors.forename: A
authors.initials: A
authors.lastname: Gullo
authors.forename: G
authors.initials: G
authors.lastname: Guarnieri
mesh_terms: D000328:Adult; D001704:Biopolymers / Q000235:genetics / Q000378:metabolism*; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*; D014947:Wounds and Injuries / Q000201:enzymology* / Q000235:genetics
chemical_list: D001704:Biopolymers; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; D025821:Polyubiquitin; D010649:Phenylalanine; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D046988:Proteasome Endopeptidase Complex