Insulin suppresses the increased activities of lysosomal cathepsins and ubiquitin conjugation system in burn-injured rats.
BACKGROUND
Burn injury results in increased rate of skeletal muscle protein degradation. In vitro studies on incubated muscles indicate that increased rate of protein degradation is due to activation of multiple proteolytic systems, but the supporting evidence is of an indirect nature. The present study was carried out to investigate the role of various lysosomal cathepsins, ubiquitin conjugation, and proteasome systems in accelerated proteolysis, and the effect of insulin in burn-induced muscle wasting syndrome.


METHODS
Fifteen to twenty percent total body surface area scald burn injury was inflicted on the shaved dorsum of young growing rats. Insulin-treated rats received a daily single subcutaneous injection for 3 days (0.25-1.0 U/day). The rate of ubiquitin conjugation to endogenous proteins and exogenously added (125)I-lysozyme and the activities of various proteases were measured in muscle homogenates.


RESULTS
Burn injury resulted in increased rate of ubiquitin conjugation to endogenous proteins and (125)I-lysozyme. Activities of cathepsins B, C, H, and L were also up-regulated following burn injury. When the burn-injured rats were treated with insulin, the increased rate of ubiquitin conjugation and cathepsin activities were suppressed to the control levels.


CONCLUSIONS
The increased ubiquitin conjugation and lysosomal cathepsins contribute to accelerated protein degradation in burn-injured rats and insulin suppresses the muscle protein degradation at least in part by suppressing the activities of lysosomal cathepsins and of ubiquitin conjugation system.
Solomon
V
V
Shriners Burns Hospital, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Madihally
S
S
Yarmush
M
M
Toner
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002056:Burns / Q000378:metabolism*; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D009097:Multienzyme Complexes / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley; D014452:Ubiquitins / Q000378:metabolism*
D007328:Insulin; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex