title: Synergistic effects of 12-O-tetradecanoylphorbol-13-acetate and dexamethasone on de novo synthesis of histidine decarboxylase in mouse mastocytoma P-815 cells.
abstract: 12-O-Tetradecanoylphorbol-13-acetate (TPA) markedly enhanced the increase in L-histidine decarboxylase (HDC) activity induced by dexamethasone in mouse mastocytoma P-815 cells, even with a concentration of the latter that had the maximal effect, whereas it induced a rapid and transient increase in HDC activity, which peaked after 3 h in the absence of dexamethasone. The synergistic effect of TPA on HDC activity induced by dexamethasone was detected after 4 h, a plateau level being reached by 6 h, which was similar to the time course with dexamethasone alone. TPA enhanced the induction of HDC activity by various glucocorticoids, but had no effect on the induction by dibutyryl cAMP, prostaglandin E2 or sodium butyrate. Both 1-oleoyl-2-acetylglycerol, a protein kinase C activator, and okadaic acid, a protein phosphatase inhibitor, enhanced the increase in HDC activity induced by dexamethasone, but 4 alpha-phorbol-12,13-didecanoate, an inactive derivative of TPA, did not. Protein kinase C inhibitors, such as staurosporin, H-7 and K255a, suppressed the increase in HDC activity induced by TPA with or without dexamethasone. The enhancement of HDC activity by dexamethasone was completely suppressed by cycloheximide or actinomycin D. Furthermore, TPA markedly enhanced the accumulation of HDC mRNA due to dexamethasone (5 to 10-fold, from 6 to 12 h after). TPA did not cause a significant increase in the level of either [3H]dexamethasone binding capacity or preformed HDC activity in cells. These results taken together suggest that dexamethasone-induced de novo synthesis of HDC in mastocytoma P-815 cells is up-regulated by TPA-activated protein kinase C through the mechanism involving an increased rate of transcription.
authors.affiliation: Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.forename: M
authors.initials: M
authors.lastname: Ohgoh
authors.forename: S
authors.initials: S
authors.lastname: Emoto
authors.forename: E
authors.initials: E
authors.lastname: Ohmori
authors.forename: N
authors.initials: N
authors.lastname: Imanishi
authors.forename: K
authors.initials: K
authors.lastname: Yatsunami
authors.forename: A
authors.initials: A
authors.lastname: Ichikawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002273:Carcinogens; D003907:Dexamethasone / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000096:biosynthesis* / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D012515:Mast-Cell Sarcoma / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D019319:Okadaic Acid; D010703:Phorbol Esters / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D004075:Diglycerides; D004988:Ethers, Cyclic; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D012333:RNA, Messenger; D019319:Okadaic Acid; C008876:phorbol-12,13-didecanoate; D003907:Dexamethasone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D006640:Histidine Decarboxylase; D013755:Tetradecanoylphorbol Acetate