Regulation of the ubiquitin proteasome system in mechanically injured human skeletal muscle.
Metabolic consequences of direct muscle trauma are insufficiently defined. Their effects on the ubiquitin-proteasome pathway (UPP) of protein degradation in human skeletal muscles are as yet unknown. Thus, we investigated whether the UPP is involved in the metabolic response evoked in directly traumatized human skeletal muscles. Biopsies were obtained from contused muscles after fractures and from normal muscles during elective implant removal (control). As estimated by western blot analyses, concentrations of free ubiquitin and ubiquitin protein conjugates were similar in extracts from injured and uninjured muscles. Ubiquitin protein ligation rates were reduced after injury (1.5+/-0.2 vs. 1.0+/-0.15 fkat/microg; p=0.04). Chymotryptic-, tryptic- and caspase-like proteasome peptidase activities (total activity minus activity in the presence of proteasome inhibitors) increased significantly after trauma (p=0.04 - 0.001). Significant increases in total chymotryptic- and caspase-like activities were attributable to proteasome activation. Our results extend the possible role of the UPP in muscle wasting to direct muscle trauma. They further suggest that the effects of direct mechanical trauma are not limited to the proteasome and imply that ubiquitin protein ligase systems are also involved. Based on the potential role of the UPP in systemic diseases, it might also be a therapeutic target to influence muscle loss in critically ill blunt trauma patients, in which large proportions of muscle are exposed to direct trauma.
Department for Trauma Surgery, University Hospital Mannheim, Ruprecht-Karls University, Heidelberg, Germany.
M
M
Seiffert
D
D
Gosenca
N
N
Ponelies
N
N
Ising
M B
MB
Patel
U
U
Obertacke
M
M
Majetschak
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D002918:Chymotrypsin / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000293:injuries* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000201:enzymology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D002918:Chymotrypsin; D014357:Trypsin; D020169:Caspases; D046988:Proteasome Endopeptidase Complex