Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle.
There is evidence that burn injury stimulates ubiquitin-proteasome-dependent protein breakdown in skeletal muscle. In this proteolytic pathway, protein substrates are conjugated to multiple molecules of ubiquitin, whereafter they are recognized, unfolded and degraded by the multicatalytic 26 S protease complex. The 20 S proteasome is the catalytic core of the 26 S protease complex. The influence of burn injury on the expression and activity of the 20 S proteasome has not been reported. We tested the hypothesis that burn injury increases 20 S proteasome activity and the expression of mRNA for the 20 S proteasome subunits RC3 and RC7. Proteolytic activity of isolated 20 S proteasomes, assessed as activity against fluorogenic peptide substrates, was increased in extensor digitorum longus muscles from burned rats. Northern-blot analysis revealed that the expression of mRNA for RC3 and RC7 was increased by 100% and 80% respectively following burn injury. Increased activity and expression of the 20 S proteasome in muscles from burned rats support the concept that burn-induced muscle cachexia is at least, in part, regulated by the ubiquitin-proteasome proteolytic pathway.
Fang
C H
CH
The Shriners Hospital for Children, Cincinnati, OH 45229, USA.
Li
B G
BG
Fischer
D R
DR
Wang
J J
JJ
Runnels
H A
HA
Monaco
J J
JJ
Hasselgren
P O
PO
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002056:Burns / Q000201:enzymology*; D002100:Cachexia / Q000503:physiopathology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex