Dynamics of tissue ubiquitin pools and ubiquitin-proteasome pathway component activities during the systemic response to traumatic shock

• Published in: Physiological research Vol. 56; no. 5; pp. 547 - 557
• Main Authors: Patel, M B, Earle, S A, Majetschak, M
• Format: Journal Article
• Language: English
• Published: Czech Republic Institute of Physiology 01.01.2007
• Subjects: Animals; Blood; Brain; Chymases - metabolism; Disease Models, Animal; Femoral Fractures - complications; Femoral Fractures - enzymology; Femoral Fractures - metabolism; Fluid Therapy; Hemorrhage; Hemorrhage - complications; Hemorrhage - enzymology; Hemorrhage - metabolism; Kidney - metabolism; Lung - metabolism; Muscle, Skeletal - metabolism; Myocardium - metabolism; Patients; Proteasome Endopeptidase Complex - metabolism; Serine Endopeptidases - metabolism; Shock, Traumatic - enzymology; Shock, Traumatic - etiology; Shock, Traumatic - metabolism; Shock, Traumatic - therapy; Spleen; Spleen - metabolism; Swine; Time Factors; Tissues; Ubiquitins - metabolism
• ISSN: 0862-8408; 1802-9973
• DOI: 10.33549/physiolres.931068

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.