Regulation of lysosomal proteolysis in burn injury.
The regulation of the lysosomal pathway by burn injury was investigated using a local burn model in which one hindlimb of a rat is scaled at 85 degrees C for 3.6 s. By two days postinjury the rate of net protein breakdown in the incubated soleus muscle from the burned leg is doubled. The activity of cathepsin D increases 40% to 50% and that of cathepsins B and L increase 80% to 100%. The activity of a lysosomal nonprotease activity, N-acetylglucosaminidase, is not significantly increased. The latency of lysosomal enzymes (an estimate of cellular autophagy) did not change at any time postburn. Inhibitors of autophagy (ie, leucine and 3-methyladenine) inhibited net protein breakdown and increased latency to a similar extent in muscles from control and burned legs. Thus, there is no evidence that a change in cellular autophagy is responsible for the increased proteolysis seen in intact muscle. However, burn-induced changes in alternative routes of protein sequestration cannot be excluded. Burn did not increase either receptor-mediated or fluid phase endocytosis by incubated soleus muscle. Burn injury also did not reduce the inhibitory action of cytoplasmic inhibitors of cathepsins B and L in skeletal muscle. However, burn injury markedly stimulated the synthesis of glycoproteins in the microsomal fraction without affecting overall protein synthesis. This increase in synthesis preceded the rise in lysosomal protease activity. These results support the possibility that induction of lysosomal protease synthesis may underlie burn-induced increases in muscle proteolysis.
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D000118:Acetylglucosaminidase / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002056:Burns / Q000201:enzymology*; D002403:Cathepsins / Q000378:metabolism; D004705:Endocytosis; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008358:Mannose / Q000378:metabolism; D009132:Muscles / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010649:Phenylalanine; C025946:3-methyladenine; D000118:Acetylglucosaminidase; D002403:Cathepsins; D010447:Peptide Hydrolases; D000225:Adenine; D008358:Mannose