Patients with sepsis in the ICU (intensive care unit) are characterized by skeletal muscle wasting. This leads to muscle dysfunction that also influences the respiratory capacity, resulting in prolonged mechanical ventilation. Catabolic conditions are associated with a general activation of the ubiquitin–proteasome pathway in skeletal muscle. The aim of the present study was to measure the proteasome proteolytic activity in both respiratory and leg muscles from ICU patients with sepsis and, in addition, to assess the variation of proteasome activity between individuals and between duplicate leg muscle biopsy specimens. When compared with a control group (n=10), patients with sepsis (n=10) had a 30% (P<0.05) and 45% (P<0.05) higher proteasome activity in the respiratory and leg muscles respectively. In a second experiment, ICU patients with sepsis (n=17) had a 55% (P<0.01) higher proteasome activity in the leg muscle compared with a control group (n=10). The inter-individual scatter of proteasome activity was larger between the patients with sepsis than the controls. We also observed a substantial intra-individual difference in activity between duplicate biopsies in several of the subjects. In conclusion, the proteolytic activity of the proteasome was higher in skeletal muscle from patients with sepsis and multiple organ failure compared with healthy controls. It was shown for the first time that respiratory and leg muscles were affected similarly. Furthermore, the variation in proteasome activity between individuals was more pronounced in the ICU patients for both muscle types, whereas the intra-individual variation between biopsies was similar for ICU patients and controls.
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May 2007
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Research Article|
April 02 2007
Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis
Maria Klaude;
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
Correspondence: Dr Maria Klaude (email [email protected]), at the Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden.
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Katarina Fredriksson;
Katarina Fredriksson
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
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Inga Tjäder;
Inga Tjäder
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
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Folke Hammarqvist;
Folke Hammarqvist
†Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
‡Gastrocentrum, Department of Surgery, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
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Bo Ahlman;
Bo Ahlman
§Centre for Gastrointestinal Disease, Karolinska Institutet, Ersta Hospital, S-11691 Stockholm, Sweden
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Olav Rooyackers;
Olav Rooyackers
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
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Jan Wernerman
Jan Wernerman
*Department of Anaesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
†Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden
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Publisher: Portland Press Ltd
Received:
September 19 2006
Revision Received:
November 22 2006
Accepted:
November 22 2006
Accepted Manuscript online:
November 22 2006
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2007
Clin Sci (Lond) (2007) 112 (9): 499–506.
Article history
Received:
September 19 2006
Revision Received:
November 22 2006
Accepted:
November 22 2006
Accepted Manuscript online:
November 22 2006
Citation
Maria Klaude, Katarina Fredriksson, Inga Tjäder, Folke Hammarqvist, Bo Ahlman, Olav Rooyackers, Jan Wernerman; Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis. Clin Sci (Lond) 1 May 2007; 112 (9): 499–506. doi: https://doi.org/10.1042/CS20060265
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