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

Creator:
Patel, M. P., Earle, S. A., and Majetschak, Matthias
Format:
print, bez média, and svazek
Type:
article, články, model:article, and TEXT
Subject:
Patologie. Klinická medicína, biochemie, traumatologie, šok (lékařství), biochemistry, traumatology, shock (medicine), proteasome endopeptidase complex, ubiquitin-protein ligase complex, ATP-dependent 26S protease, epoxomicin, 14, and 616
Language:
English
Description:
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., M. B. Patel, S. A. Earle, M. Majetschak., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public