Prostaglandin E 2 and muscle protein turnover in Pseudomonas aeruginosa sepsis

Abstract

Rats were injected intraperitoneally with Pseudomonas aeruginosa (septic group) or sterile 0.9% NaCl (controls). Soleus muscles were excised 7 h later, and muscle prostaglandin E 2 release and tyrosine release were measured in vitro. Muscles of septic rats exhibited 226–326% higher release of prostaglandin E 2 and 54–84% higher net proteolysis than muscles of controls. Inclusion of aspirin or indomethacin in the incubation medium almost completely inhibited prostaglandin E 2 production, but had no effect on net proteolysis in muscles from either group. Inclusion of cycloheximide, a protein synthesis inhibitor, increased tyrosine release of control muscles by 42%, whereas no statistically significant increase was observed in muscles from infected rats. However, total proteolytic rate, indexed by tyrosine release in the presence of cycloheximide, was 22% higher in muscles of septic rats compared to that of control animals. Concomitantly, inclusion of cycloheximide inhibited prostaglandin E 2 release by muscles of infected rats by 91% and that of controls by 65%. It is concluded that (a) muscles of septic animals exhibit a pronounced stimulation of prostaglandin E 2 release and net proteolysis, combined with a small increase in total proteolytic rate, (b) the stimulation of net proteolysis is mainly due to inhibition of protein synthesis, (c) the increases in net and total proteolysis appear to be independent of prostaglandin E 2 production, (d) cycloheximide has a previously unrecognized inhibitory effect on muscle prostaglandin E 2 production.