Insulin-like growth factor-I inhibits lysosomal and proteasome-dependent proteolysis in skeletal muscle after burn injury.
Previous studies suggest that insulin-like growth factor-I (IGF-I) inhibits burn-induced muscle wasting mainly by reducing muscle protein degradation. The intracellular mechanisms of this effect of IGF-I are not known. In the present study, we examined the influence of IGF-I on individual proteolytic pathways in muscles from burned rats. Extensor digitorum longus muscles from burned rats were incubated with specific blockers of lysosomal, calcium-calpain-dependent, and ubiquitin-proteasome-dependent proteolytic pathways in the absence or presence of IGF-I. In addition, cathepsin B and L activities and 20S proteasome activity were determined. IGF-I inhibited lysosomal and ubiquitin-proteasome-dependent protein breakdown in skeletal muscle from burned rats by 70 and 90%, respectively, but did not influence calcium-calpain-dependent protein breakdown. The hormone blocked the burn-induced increase in cathepsin B and L activities but did not reduce 20S proteasome activity. Results are important because they provide novel information about intracellular mechanisms by which IGF-I inhibits the catabolic response to burn injury in skeletal muscle.
D000818:Animals; D002056:Burns / Q000201:enzymology*; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects*; D008297:Male; D009097:Multienzyme Complexes / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology* / Q000293:injuries; D010447:Peptide Hydrolases / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015599:Trauma Severity Indices
D009097:Multienzyme Complexes; D007334:Insulin-Like Growth Factor I; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex