Ubiquitin-proteasome-dependent proteolytic activity remains elevated after zymosan-induced sepsis in rats while muscle mass recovers.
We studied the role of the ubiquitin-proteasome system in rat skeletal muscle during sepsis and subsequent recovery. Sepsis was induced with intraperitoneal zymosan injections. This model allows one to study a sustained and reversible catabolic phase and mimics the events that prevail in septic and subsequently recovering patients. In addition, the role of the ubiquitin-proteasome system during muscle recovery is poorly documented. There was a trend for increased ubiquitin-conjugate formation in the muscle wasting phase, which was abolished during the recovery phase. The trypsin- and chymotrypsin-like peptidase activities of the 20S proteasome peaked at day 6 following zymosan injection (i.e. when both muscle mass and muscle fiber cross-sectional area were reduced the most), but remained elevated when muscle mass and muscle fiber cross-sectional area were recovering (11 days). This clearly suggests a role for the ubiquitin-proteasome pathway in the muscle remodeling and/or recovery process. Protein levels of 19S complex and 20S proteasome subunits did not increase throughout the study, pointing to alternative mechanisms regulating proteasome activities. Overall these data support a role for ubiquitin-proteasome dependent proteolysis in the zymosan septic model, in both the catabolic and muscle recovery phases.
Minnaard
R
R
Nutrition and Toxicology Research Institute Maastricht, Department of Movement Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Ronnie.Minnaard@bw.unimaas.nl
Wagenmakers
A J M
AJ
Combaret
L
L
Attaix
D
D
Drost
M R
MR
van Kranenburg
G P
GP
Schaart
G
G
Hesselink
M K C
MK
D000818:Animals; D001835:Body Weight; D002918:Chymotrypsin / Q000378:metabolism; D004435:Eating; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology*
D021122:Protein Subunits; D025801:Ubiquitin; D015054:Zymosan; D002918:Chymotrypsin; D046988:Proteasome Endopeptidase Complex