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

Patel MB, Earle SA, Majetschak M
Physiol Res. 2007 56 (5): 547-57

PMID: 17184142

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.

MeSH Terms (17)

Animals Chymases Disease Models, Animal Femoral Fractures Fluid Therapy Hemorrhage Kidney Lung Muscle, Skeletal Myocardium Proteasome Endopeptidase Complex Serine Endopeptidases Shock, Traumatic Spleen Swine Time Factors Ubiquitins

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