Prostaglandin E2 and muscle proteolysis: effect of burn injury and cycloheximide.
Rats were subjected to a single hindlimb scald, and 3 days later soleus muscles from the burned and contralateral unburned hindlimbs were studied in vitro. Burned limb muscle released 354% more prostaglandin E2 (PGE2) and 119% more tyrosine than the contralateral uninjured counterpart. Neither the rate of net proteolysis in the uninjured muscle nor the stimulated net proteolysis in the burned limb muscle could be reduced by 90% inhibition of PGE2 production with aspirin or indomethacin. Inhibition of tissue protein synthesis with 5 X 10(-5) M cycloheximide stimulated tyrosine release by soleus muscles of both hindlimbs, but the increment in the burned limb muscle was 167% greater than in the contralateral uninjured counterpart. Concomitantly, cycloheximide decreased PGE2 releases by injured and uninjured muscles 90 and 73%, respectively. This previously unrecognized action of cycloheximide was investigated in soleus muscles of normal uninjured rats. It was found that 1 X 10(-6) M cycloheximide produces a 70% inhibition of muscle PGE2 release and increasing the concentration of inhibitor up to 500-fold does not further decrease PGE2 production. Cycloheximide acts by reducing the availability of endogenous arachidonic acid for PGE2 synthesis.
McKinley
C J
CJ
Turinsky
J
J
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002056:Burns / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000378:metabolism
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D011506:Proteins; D016718:Arachidonic Acid; D014443:Tyrosine; D003513:Cycloheximide; D015232:Dinoprostone