Abstract
Previous studies showed that phorbol esters and thyrotropin-releasing hormone (TRH) stimulated phosphatidylcholine synthesis via protein kinase C in GH3 pituitary cells [Kolesnick (1987) J. Biol. Chem. 262, 14525-14530]. In contrast, 1,2-diacylglycerol-stimulated phosphatidylcholine synthesis appeared independent of protein kinase C. The present studies compare phosphatidylcholine synthesis stimulated by these agents with inhibition via the cyclic AMP system. The potent phorbol ester phorbol 12-myristate 13-acetate (PMA, 10 nM) increased [32P]Pi incorporation into phosphatidylcholine at 30 min to 159 +/- 6% of control. The adenylate cyclase activator cholera toxin (CT; 10 nM) and the cyclic AMP analogue dibutyryl cyclic AMP (1 mM) abolished this effect. CT similarly abolished TRH-induced phosphatidylcholine, but not phosphatidylinositol, synthesis. This is the first report of inhibiton of receptor-mediated phosphatidylcholine synthesis by the cyclic AMP system. The 1,2-diacylglycerol 1,2-dioctanoylglycerol (diC8) also stimulated concentration-dependent phosphatidylcholine synthesis. DiC8 (3 micrograms/ml) induced an effect quantitatively similar to that of maximal concentrations of PMA and TRH, whereas a maximal diC8 concentration (30 micrograms/ml) stimulated an effect 3-4-fold greater than these other agents. CT decreased the effect of diC8 (3 micrograms/ml) by 80%. Higher diC8 concentrations overcame the CT inhibition. Similar results were obtained with dibutyryl cyclic AMP. Additional differences were found between low and high concentrations of diC8. Low concentrations of diC8 failed to induce additive phosphatidylcholine synthesis with maximal concentrations of PMA, whereas high concentrations were additive. Hence, low concentrations of 1,2-diacylglycerols appear to be regulated similarly to phorbol esters, and higher concentrations appear to act via a pathway unavailable to phorbol esters.
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Selected References
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- Bass D. A., Gerard C., Olbrantz P., Wilson J., McCall C. E., McPhail L. C. Priming of the respiratory burst of neutrophils by diacylglycerol. Independence from activation or translocation of protein kinase C. J Biol Chem. 1987 May 15;262(14):6643–6649. [PubMed] [Google Scholar]
- Berridge M. J. The molecular basis of communication within the cell. Sci Am. 1985 Oct;253(4):142–152. doi: 10.1038/scientificamerican1085-142. [DOI] [PubMed] [Google Scholar]
- Gourdji D., Bataille D., Vauclin N., Grouselle D., Rosselin G., Tixier-Vidal A. Vasoactive intestinal peptide (VIP) stimulates prolactin (PRL) release and cAMP production in a rat pituitary cell line (GH3/B6). Additive effects of VIP and TRH on PRL release. FEBS Lett. 1979 Aug 1;104(1):165–168. doi: 10.1016/0014-5793(79)81107-2. [DOI] [PubMed] [Google Scholar]
- Hannun Y. A., Bell R. M. Lysosphingolipids inhibit protein kinase C: implications for the sphingolipidoses. Science. 1987 Feb 6;235(4789):670–674. doi: 10.1126/science.3101176. [DOI] [PubMed] [Google Scholar]
- Imai A., Gershengorn M. C. Evidence for tight coupling of thyrotropin-releasing hormone receptors to stimulated inositol trisphosphate formation in rat pituitary cells. J Biol Chem. 1985 Sep 5;260(19):10536–10540. [PubMed] [Google Scholar]
- Kolesnick R. N. 1,2-Diacylglycerols but not phorbol esters stimulate sphingomyelin hydrolysis in GH3 pituitary cells. J Biol Chem. 1987 Dec 15;262(35):16759–16762. [PubMed] [Google Scholar]
- Kolesnick R. N., Clegg S. 1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase. J Biol Chem. 1988 May 15;263(14):6534–6537. [PubMed] [Google Scholar]
- Kolesnick R. N., Paley A. E. 1,2-Diacylglycerols and phorbol esters stimulate phosphatidylcholine metabolism in GH3 pituitary cells. Evidence for separate mechanisms of action. J Biol Chem. 1987 Jul 5;262(19):9204–9210. [PubMed] [Google Scholar]
- Kolesnick R. N. Sphingomyelinase action inhibits phorbol ester-induced differentiation of human promyelocytic leukemic (HL-60) cells. J Biol Chem. 1989 May 5;264(13):7617–7623. [PubMed] [Google Scholar]
- Kolesnick R. N. Thyrotropin-releasing hormone and phorbol esters induce phosphatidylcholine synthesis in GH3 pituitary cells. Evidence for stimulation via protein kinase C. J Biol Chem. 1987 Oct 25;262(30):14525–14530. [PubMed] [Google Scholar]
- Kreutter D., Caldwell A. B., Morin M. J. Dissociation of protein kinase C activation from phorbol ester-induced maturation of HL-60 leukemia cells. J Biol Chem. 1985 May 25;260(10):5979–5984. [PubMed] [Google Scholar]
- Lacal J. C., Moscat J., Aaronson S. A. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene. Nature. 1987 Nov 19;330(6145):269–272. doi: 10.1038/330269a0. [DOI] [PubMed] [Google Scholar]
- Liscovitch M., Slack B., Blusztajn J. K., Wurtman R. J. Differential regulation of phosphatidylcholine biosynthesis by 12-O-tetradecanoylphorbol-13-acetate and diacylglycerol in NG108-15 neuroblastoma x glioma hybrid cells. J Biol Chem. 1987 Dec 25;262(36):17487–17491. [PubMed] [Google Scholar]
- Nishizuka Y. Perspectives on the role of protein kinase C in stimulus-response coupling. J Natl Cancer Inst. 1986 Mar;76(3):363–370. [PubMed] [Google Scholar]
- Paddon H. B., Vance D. E. Tetradecanoyl-phorbol acetate stimulates phosphatidylcholine biosynthesis in HeLa cells by an increase in the rate of the reaction catalyzed by CTP:phosphocholine cytidylyltransferase. Biochim Biophys Acta. 1980 Dec 5;620(3):636–640. doi: 10.1016/0005-2760(80)90156-3. [DOI] [PubMed] [Google Scholar]
- Pelech S. L., Paddon H. B., Vance D. E. Phorbol esters stimulate phosphatidylcholine biosynthesis by translocation of CTP:phosphocholine cytidylyltransferase from cytosol to microsomes. Biochim Biophys Acta. 1984 Oct 4;795(3):447–451. doi: 10.1016/0005-2760(84)90171-1. [DOI] [PubMed] [Google Scholar]
- Pelech S. L., Pritchard P. H., Brindley D. N., Vance D. E. Fatty acids reverse the cyclic AMP inhibition of triacylglycerol and phosphatidylcholine synthesis in rat hepatocytes. Biochem J. 1983 Oct 15;216(1):129–136. doi: 10.1042/bj2160129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pelech S. L., Pritchard P. H., Vance D. E. cAMP analogues inhibit phosphatidylcholine biosynthesis in cultured rat hepatocytes. J Biol Chem. 1981 Aug 25;256(16):8283–8286. [PubMed] [Google Scholar]
- Pelech S. L., Vance D. E. Regulation of phosphatidylcholine biosynthesis. Biochim Biophys Acta. 1984 Jun 25;779(2):217–251. doi: 10.1016/0304-4157(84)90010-8. [DOI] [PubMed] [Google Scholar]
- Pelech S. L., Vance D. E. Regulation of rat liver cytosolic CTP: phosphocholine cytidylyltransferase by phosphorylation and dephosphorylation. J Biol Chem. 1982 Dec 10;257(23):14198–14202. [PubMed] [Google Scholar]
- Preiss J., Loomis C. R., Bishop W. R., Stein R., Niedel J. E., Bell R. M. Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells. J Biol Chem. 1986 Jul 5;261(19):8597–8600. [PubMed] [Google Scholar]
- Rebecchi M. J., Kolesnick R. N., Gershengorn M. C. Thyrotropin-releasing hormone stimulates rapid loss of phosphatidylinositol and its conversion to 1,2-diacylglycerol and phosphatidic acid in rat mammotropic pituitary cells. Association with calcium mobilization and prolactin secretion. J Biol Chem. 1983 Jan 10;258(1):227–234. [PubMed] [Google Scholar]
- Sanghera J. S., Vance D. E. CTP:phosphocholine cytidylyltransferase is a substrate for cAMP-dependent protein kinase in vitro. J Biol Chem. 1989 Jan 15;264(2):1215–1223. [PubMed] [Google Scholar]
- Strålfors P. Insulin stimulation of glucose uptake can be mediated by diacylglycerol in adipocytes. Nature. 1988 Oct 6;335(6190):554–556. doi: 10.1038/335554a0. [DOI] [PubMed] [Google Scholar]
- Yamamoto S., Gotoh H., Aizu E., Kato R. Failure of 1-oleoyl-2-acetylglycerol to mimic the cell-differentiating action of 12-O-tetradecanoylphorbol 13-acetate in HL-60 cells. J Biol Chem. 1985 Nov 15;260(26):14230–14234. [PubMed] [Google Scholar]
