Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis

Patients with sepsis in the intensive care unit (ICU) are characterised by skeletal muscle wasting. This leads to muscle dysfunction that also influences the respiratory capacity leading to prolonged mechanical ventilation. Catabolic conditions are associated with a general activation of the ubiquitin proteasome pathway in skeletal muscle. In the present study, the aim 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. As compared to 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 muscle respectively. In a second experiment ICU patients with sepsis (n=17) showed a 55 % (p<0.01) higher proteasome activity in the leg muscle as compared to a control group (n=10). The inter-individual scatter of proteasome activity was larger between the patients with sepsis than between 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 as compared to healthy controls. It was shown for the first time that respiratory and leg muscles were affected similarly. Furthermore, the variation of proteasome activity between individuals was more pronounced in the ICU patients for both muscle types, while the intra-individual variation between biopsies was similar for ICU patients and controls. ; maria.klaude@ki.se (Klaude, Maria) ; Anaesthesiology & Intensive Care, Karolinska University Hospital Huddinge - SWEDEN (Klaude, Maria) ; SWEDEN