Glucocorticoid-mediated increases in glycerol phosphate dehydrogenase activity is inhibited by the phorbol ester tumor promoters.
An oligodendroglial specific property, glucocorticoid regulation of glycerol-3-phosphate dehydrogenase (GPDH) levels, was inhibited in C6 rat glioma cells when 4 beta-phorbol 12-myristate 13-acetate (PMA) was added to the cultures. PMA inhibited GPDH induction in both logarithmic- and stationary-phase cells. These events are most likely mediated through the phorbol ester receptor since the ability of various phorbol ester analogs to compete with the ligand [3H]4 beta-phorbol 12,13-dibutyrate for binding to the receptor correlates with the ability the particular analog has to inhibit GPDH induction. Additionally, like tumor promotion in vivo, the inhibition of GPDH induction is reversible. The PMA effect is not restricted to the C6 cell line since PMA also inhibits GPDH inducibility in another rat glioma cell line. This PMA-mediated event has been partially characterized. PMA did not affect the overall rate of protein or RNA synthesis. It was ineffective in altering both glucocorticoid accumulation to the nucleus and the rate of GPDH degradation. It appears likely that PMA's inhibitory action occurs at the transcriptional or translational level.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction; D005910:Glioma / Q000201:enzymology; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis*; D009836:Oligodendroglia / Q000187:drug effects / Q000201:enzymology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D051381:Rats; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010703:Phorbol Esters; D010704:Phorbols; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D003907:Dexamethasone; D013806:Theophylline; D005993:Glycerolphosphate Dehydrogenase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate