Muscle wasting negatively affects morbidity and mortality in critically ill patients. This progressive wasting is accompanied by, in general, a normal muscle PS (protein synthesis) rate. In the present study, we investigated whether muscle protein degradation is increased in critically ill patients with sepsis and which proteolytic enzyme systems are involved in this degradation. Eight patients and seven healthy volunteers were studied. In vivo muscle protein kinetics was measured using arteriovenous balance techniques with stable isotope tracers. The activities of the major proteolytic enzyme systems were analysed in combination with mRNA expression of genes related to these proteolytic systems. Results show that critically ill patients with sepsis have a variable but normal muscle PS rate, whereas protein degradation rates are dramatically increased (up to 160%). Of the major proteolytic enzyme systems both the proteasome and the lysosomal systems had higher activities in the patients, whereas calpain and caspase activities were not changed. Gene expression of several genes related to the proteasome system was increased in the patients. mRNA levels of the two main lysosomal enzymes (cathepsin B and L) were not changed but, conversely, genes related to calpain and caspase had a higher expression in the muscles of the patients. In conclusion, the dramatic muscle wasting seen in critically ill patients with sepsis is due to increased protein degradation. This is facilitated by increased activities of both the proteasome and lysosomal proteolytic systems.
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Research Article|
October 11 2011
Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis
Maria Klaude;
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology and Clinical Physiology, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
Correspondence: Dr Maria Klaude (email maria.klaude@ki.se).
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Maiko Mori;
Maiko Mori
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology and Clinical Physiology, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
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Inga Tjäder;
Inga Tjäder
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology and Clinical Physiology, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
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Thomas Gustafsson;
Thomas Gustafsson
‡Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
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Jan Wernerman;
Jan Wernerman
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology and Clinical Physiology, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
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Olav Rooyackers
Olav Rooyackers
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology and Clinical Physiology, Karolinska University Hospital Huddinge, Karolinska Institutet, S-14186 Stockholm, Sweden
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Publisher: Portland Press Ltd
Received:
May 09 2011
Revision Received:
August 25 2011
Accepted:
August 31 2011
Accepted Manuscript online:
August 31 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 122 (3): 133–142.
Article history
Received:
May 09 2011
Revision Received:
August 25 2011
Accepted:
August 31 2011
Accepted Manuscript online:
August 31 2011
Citation
Maria Klaude, Maiko Mori, Inga Tjäder, Thomas Gustafsson, Jan Wernerman, Olav Rooyackers; Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis. Clin Sci (Lond) 1 February 2012; 122 (3): 133–142. doi: https://doi.org/10.1042/CS20110233
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