Human septic myopathy: induction of cyclooxygenase, heme oxygenase and activation of the ubiquitin proteolytic pathway.
BACKGROUND
Skeletal muscle failure and wasting are manifestations of sepsis in humans that leads to serious and prolonged complications. The authors investigated the role of the major proinflammatory and antiinflammatory pathways, namely the inducible isoforms cyclooxygenase (COX-2) and heme oxygenase (HO-1), and the ubiquitin proteolytic pathway in skeletal muscle of septic patients.


METHODS
Protein expression was detected by Western blot techniques. Muscle biopsies were taken from two muscle groups, rectus abdominis and vastus lateralis, of septic and control patients.


RESULTS
The study showed an increase in COX-2 and HO-1 proteins expression and an activation of the proteolytic ubiquitin pathway with a parallel increase in free ubiquitin and ubiquitinated proteins in skeletal muscle of septic but not of control patients. In addition, those patients who would die from septic shock expressed more COX-2 and HO-1 proteins in muscle biopsies than did those patients who would survive.


CONCLUSIONS
This study showed a marked involvement of local proinflammatory and antiinflammatory pathways and, more importantly, demonstrated the existence of an active ubiquitin proteolytic pathway in skeletal muscle of septic patients. Activation of ubiquitin pathway could be involved in sepsis-related muscle catabolism and wasting.
Department of Anesthesiology and Critical Care Medicine, Institut National de la Santé et de la Recherche Médicale (INSERM) U572, Paris, France.
Christophe
C
Rabuel
Estelle
E
Renaud
David
D
Brealey
Philippe
P
Ratajczak
Thibaut
T
Damy
Arnaud
A
Alves
Aïda
A
Habib
Mervyn
M
Singer
Didier
D
Payen
Alexandre
A
Mebazaa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D010450:Endopeptidases / Q000378:metabolism; D004790:Enzyme Induction / Q000502:physiology; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009135:Muscular Diseases / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D018805:Sepsis / Q000150:complications* / Q000201:enzymology / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D007527:Isoenzymes; D008565:Membrane Proteins; D025801:Ubiquitin; D006419:Heme Oxygenase (Decyclizing); D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010450:Endopeptidases