Dexamethasone blocks arachidonate biosynthesis in isolated hepatocytes and cultured hepatoma cells.
The effect of dexamethasone on the incorporation and conversion of [1-14C]eicosa-8,11,14-trienoic acid to arachidonic acid in isolated hepatocytes and in hepatoma tissue culture (HTC) cells was studied. In both kinds of cells, no changes in the exogenous acid incorporation were found when the hormone was added to the incubation media at 0.1 or 0.2 mM concentration, while the biosynthesis of arachidonic acid was significantly depressed. The effect on the biosynthesis was faster in isolated normal liver cells (60 min) than in tumoral cells (120 min) and reached an inhibition of ca. 50% after 3 hr of treatment. The addition of cycloheximide (10(-6) M) also caused a marked decrease in the biosynthesis of this polyunsaturated fatty acid, but when dexamethasone was added to the media simultaneously with cycloheximide, a synergistic action was not observed. The results obtained show that protein synthesis would be involved in the modulation of the biosynthesis of arachidonic acid by glucocorticoids. The changes in the delta 5 desaturation of labeled 20:3 omega 6 to arachidonic acid correlated with changes in the fatty acid composition in isolated cells.
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D016718:Arachidonic Acid; D003907:Dexamethasone; D015126:8,11,14-Eicosatrienoic Acid