Effect of inhibitors of proteolysis and arachidonic acid metabolism on burn-induced protein breakdown.
A rat model has been developed to study the local effects of burn injury on the underlying muscle tissue. Protein turnover was measured in soleus muscle incubated in vitro in which both tyrosine release and protein synthesis was measured. A scald injury (3 seconds) to a small area of one hindlimb produces an increase in muscle proteolysis and is without effect on the soleus muscle of the contralateral leg. A very high concentration of indomethacin (40 mumol/L) had no effect on proteolysis in the control muscle but specifically inhibited burn-induced protein breakdown. However, since other cyclooxygenase inhibitors (aspirin and ibuprofen), lipoxygenase inhibitors (ETYA, NDGA, and esculetin), and mepacrine (a phospholipase inhibitor) had no effect on protein breakdown, it is unlikely that a product of arachidonic acid metabolism maintains the increased proteolysis in vitro. In addition, endogenous production of prostaglandin E2 (PGE2) was not different in muscles from burned and control legs. Probes of the proteolytic pathway using inhibitors show that the burn-induced stimulation of proteolysis is consistent with the stimulation of lysosomal protease activity. These results are supported by the observation of increased acid protease activity in muscle homogenates from the burned leg. The best hypothesis that explains these data is that a lysosomal pathway of protein degradation may be enhanced by burn. Products of arachidonic acid metabolism do not appear to maintain burn-induced proteolysis in muscle, although their role in initiating the pathological changes in vivo cannot be excluded.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002056:Burns / Q000378:metabolism*; D006614:Hindlimb; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D009132:Muscles / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000032:analysis
D001095:Arachidonic Acids; D007976:Leupeptins; D009842:Oligopeptides; D011480:Protease Inhibitors; D011506:Proteins; D016718:Arachidonic Acid; D014443:Tyrosine; C002101:chymostatin; D010447:Peptide Hydrolases; D011796:Quinacrine; C032854:leupeptin; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin