Post-transcriptional inhibition of glutamine synthetase induction in rat liver epithelial cells exerted by conditioned medium from rat hepatocytes

Recently, a soluble factor produced by primary periportal hepatocytes and d ifferent from glutamine was found to completely block induction of glutamin e synthetase (GS) by dexamethasone (DEX) in the liver cell line RL-ET-1G. U sing Northern and Western blotting we investigated whether this block is re gulated on the transcriptional or the post-transcriptional level. Three dif ferent species of GS mRNA were detected that all increased (though in diffe rent proportions), when the cells were exposed to DEX for 24h. Further main tenance for another 24 h in normal DEX-containing culture medium, condition ed medium from primary periportal hepatocytes or medium containing glutamin e did not result in significant differences in GS mRNA levels. In contrast, GS protein and specific GS-activity remained high only under normal cultur e conditions, whereas both returned to basal levels in conditioned and glut amine-supplemented culture medium. Throughout, GS protein content and speci fic GS-activity strongly correlated (r = 0,98) excluding that GS-activity i s regulated by chemical modification. These data suggest that the decrease in enzyme activity caused by cultivation in CM is controlled on the post-tr anscriptional level. (C) 2000 Elsevier Science Inc. All rights reserved.