Dynamics of tissue ubiquitin pools and ubiquitin-proteasome pathway component activities during the systemic response to traumatic shock.
Based on the biological significance of the ubiquitin-proteasome pathway (UPP) and its potential role during sepsis, burns and ischemia-reperfusion injury, we hypothesized that the systemic response to traumatic shock (TS) is accompanied by tissue-specific UPP alterations. Therefore, we studied tissue ubiquitin pools, chymotryptic- and tryptic-like proteasome peptidase activities and ubiquitin-protein ligation (UbPL) rates in skeletal muscle, heart, lung, liver, spleen and kidney using a clinically relevant porcine model (bilateral femur fracture/hemorrhage followed by fluid resuscitation). TS induced a systemic reduction of tissue-specific high molecular mass ubiquitin-protein conjugates (>50 kDa). Free ubiquitin was unaffected. The dynamic organ patterns of ubiquitin pools paralleled the typical physiological response to TS and resuscitation. Reduction of ubiquitin-protein conjugates was most pronounced in heart and lung (p<0.05 vs. control) and accompanied by significant increases in proteasome peptidase and UbPL activities in these organs. Unlike all other tissues, spleen proteasome peptidase and UbPL activities were significantly reduced 10 h after TS. These findings support the concept that the UPP could play an important role in regulation of cell functions during the early whole-body response to TS. The UPP might be a therapeutic target to improve the metabolic care after TS, particularly in the heart, lung, and spleen.
Patel
M B
MB
DeWitt Daughtry Family Department of Surgery, Division of Trauma and Surgical Critical Care, University of Miami Miller School of Medicine, Miami, USA.
Earle
S A
SA
Majetschak
M
M
D000818:Animals; D053818:Chymases / Q000378:metabolism; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000150:complications* / Q000201:enzymology / Q000378:metabolism; D005440:Fluid Therapy; D006470:Hemorrhage / Q000150:complications* / Q000201:enzymology / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D012774:Shock, Traumatic / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D013154:Spleen / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014452:Ubiquitins / Q000378:metabolism*
D014452:Ubiquitins; D012697:Serine Endopeptidases; D053818:Chymases; D046988:Proteasome Endopeptidase Complex