Regulation of synthesis and activity of NAD(+)-dependent 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) by dexamethasone and phorbol ester in human erythroleukemia (HEL) cells.
Dexamethasone stimulated 15-PGDH activity in HEL cells in a time and concentration dependent manner. Increase in 15-PGDH activity by dexamethasone was found to be accompanied by an increase in enzyme synthesis as revealed by Western blot and [35S]methionine labeling studies. In addition to dexamethasone, other anti-inflammatory steroids also increased 15-PGDH activity in the order of their glucocorticoid activity. Among sex steroids only progesterone increased significantly 15-PGDH activity. 12-0-Tetradecanoylphorbol-13-acetate (TPA) also induced the synthesis of 15-PGDH but inhibited the enzyme activity. It appears that TPA caused a time dependent inactivation of 15-PGDH by a protein kinase C mediated mechanism.
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Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
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D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008715:Methionine / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology*; D013462:Sulfur Radioisotopes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D010703:Phorbol Esters; D013256:Steroids; D013462:Sulfur Radioisotopes; D009243:NAD; C008876:phorbol-12,13-didecanoate; D003907:Dexamethasone; D008715:Methionine; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate