Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1987 Feb 1;241(3):917–921. doi: 10.1042/bj2410917

Stimulation of adipocyte phospholipid methyltransferase activity by phorbol 12-myristate 13-acetate. Differential regulation of phospholipid methyltransferase and lipolysis.

K L Kelly
PMCID: PMC1147648  PMID: 3297041

Abstract

The present studies demonstrate that treatment of rat adipocytes with the phorbol ester phorbol 12-myristate 13-acetate (PMA) causes a dose-dependent stimulation of phospholipid methyltransferase (PLMT) activity. The stimulatory effect of PMA was not additive with that of isoprenaline or forskolin. The sensitivity of stimulated PLMT activity to inhibition by insulin, however, was decreased in the presence of PMA. The inhibitory effect of a maximal concentration of insulin on PLMT was unchanged in the presence of PMA. In contrast with the effects on PLMT, the lipolytic response of adipocytes to isoprenaline and the anti-lipolytic response to insulin were unaffected by PMA. These data suggest that PLMT is, whereas hormone-sensitive lipase is not, an intracellular target for the action of PMA. The lack of effect of PMA on lipolysis suggests that PLMT and hormone-sensitive lipase can be regulated by separate mechanisms. Furthermore, phorbol esters do not interfere in the regulatory pathway whereby insulin inhibits PMLT or lipolysis.

Full text

PDF
917

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alemany S., Varela I., Harper J. F., Mato J. M. Calmodulin regulation of phospholipid and fatty acid methylation by rat liver microsomes. J Biol Chem. 1982 Aug 25;257(16):9249–9251. [PubMed] [Google Scholar]
  2. Alemany S., Varela I., Mato J. M. Stimulation by vasopressin and angiotensin of phospholipid methyltransferase in isolated rat hepatocytes. FEBS Lett. 1981 Nov 30;135(1):111–114. doi: 10.1016/0014-5793(81)80955-6. [DOI] [PubMed] [Google Scholar]
  3. Ashendel C. L., Staller J. M., Boutwell R. K. Identification of a calcium- and phospholipid- dependent phorbol ester binding activity in the soluble fraction of mouse tissues. Biochem Biophys Res Commun. 1983 Feb 28;111(1):340–345. doi: 10.1016/s0006-291x(83)80157-0. [DOI] [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. Belfrage P., Fredrikson G., Nilsson N. O., Strålfors P. Regulation of adipose tissue lipolysis: phosphorylation of hormones sensitive lipase in intact rat adipocytes. FEBS Lett. 1980 Feb 25;111(1):120–124. doi: 10.1016/0014-5793(80)80775-7. [DOI] [PubMed] [Google Scholar]
  6. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  7. Castaño J. G., Alemany S., Nieto A., Mato J. M. Activation of phospholipid methyltransferase by glucagon in rat hepatocytes. J Biol Chem. 1980 Oct 10;255(19):9041–9043. [PubMed] [Google Scholar]
  8. Denton R. M., Hughes W. A. Pyruvate dehydrogenase and the hormonal regulation of fat synthesis in mammalian tissues. Int J Biochem. 1978;9(8):545–552. doi: 10.1016/0020-711x(78)90113-1. [DOI] [PubMed] [Google Scholar]
  9. Geelen M. J., Groener J. E., De Haas C. G., Van Golde L. M. Influence of glucagon on the synthesis of phosphatidylcholines and phosphatidylethanolamines in monolayer cultures of rat hepatocytes. FEBS Lett. 1979 Sep 1;105(1):27–30. doi: 10.1016/0014-5793(79)80880-7. [DOI] [PubMed] [Google Scholar]
  10. Gil M. G., Alemany S., Cao D. M., Castano J. G., Mato J. M. Calmodulin modulates phospholipid methylation in Dictyostelium discoideum. Biochem Biophys Res Commun. 1980 Jun 30;94(4):1325–1330. doi: 10.1016/0006-291x(80)90564-1. [DOI] [PubMed] [Google Scholar]
  11. Hall M., Taylor S. J., Saggerson E. D. Persistent activity modification of phosphatidate phosphohydrolase and fatty acyl-CoA synthetase on incubation of adipocytes with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate. FEBS Lett. 1985 Jan 7;179(2):351–354. doi: 10.1016/0014-5793(85)80549-4. [DOI] [PubMed] [Google Scholar]
  12. Kelly K. L., Wong E. H., Jarett L. Adrenocorticotropic stimulation and insulin inhibition of adipocyte phospholipid methylation. J Biol Chem. 1985 Mar 25;260(6):3640–3644. [PubMed] [Google Scholar]
  13. Kikkawa U., Takai Y., Minakuchi R., Inohara S., Nishizuka Y. Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties. J Biol Chem. 1982 Nov 25;257(22):13341–13348. [PubMed] [Google Scholar]
  14. Koontz J. W., Goodman S. Phorbol ester inhibition of hormonal induction of tyrosine aminotransferase. Biochem Biophys Res Commun. 1985 Sep 16;131(2):815–820. doi: 10.1016/0006-291x(85)91312-9. [DOI] [PubMed] [Google Scholar]
  15. Kraus-Friedmann N., Zimniak P. Glucagon and epinephrine-stimulated phospholipid methylation in hepatic microsomes. Life Sci. 1981 Mar 30;28(13):1483–1488. doi: 10.1016/0024-3205(81)90380-5. [DOI] [PubMed] [Google Scholar]
  16. Kuo J. F., Andersson R. G., Wise B. C., Mackerlova L., Salomonsson I., Brackett N. L., Katoh N., Shoji M., Wrenn R. W. Calcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7039–7043. doi: 10.1073/pnas.77.12.7039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lapetina E. G., Michell R. H. Stimulation by acetylcholine of phosphatidylinositol labelling. Subcellular distribution in rat cerebral-cortex slices. Biochem J. 1972 Mar;126(5):1141–1147. doi: 10.1042/bj1261141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marin-Cao D., Alvarez Chiva V., Mato J. M. Beta-adrenergic control of phosphatidylcholine synthesis by transmethylation in hepatocytes from juvenile, adult and adrenalectomized rats. Biochem J. 1983 Dec 15;216(3):675–680. doi: 10.1042/bj2160675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mérida I., Varela I., Alvarez J. F., Cabrero C., Mato J. M. Vasopressin-stimulated phosphorylation of rat liver phospholipid methyltransferase in isolated hepatocytes. FEBS Lett. 1986 Feb 17;196(2):274–278. doi: 10.1016/0014-5793(86)80262-9. [DOI] [PubMed] [Google Scholar]
  20. Niedel J. E., Kuhn L. J., Vandenbark G. R. Phorbol diester receptor copurifies with protein kinase C. Proc Natl Acad Sci U S A. 1983 Jan;80(1):36–40. doi: 10.1073/pnas.80.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nieto A., Catt K. J. Hormonal activation of phospholipid methyltransferase in the Leydig cell. Endocrinology. 1983 Aug;113(2):758–762. doi: 10.1210/endo-113-2-758. [DOI] [PubMed] [Google Scholar]
  22. Nilsson N. O., Strålfors P., Fredrikson G., Belfrage P. Regulation of adipose tissue lipolysis: effects of noradrenaline and insulin on phosphorylation of hormone-sensitive lipase and on lipolysis in intact rat adipocytes. FEBS Lett. 1980 Feb 25;111(1):125–130. doi: 10.1016/0014-5793(80)80776-9. [DOI] [PubMed] [Google Scholar]
  23. RODBELL M. METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. J Biol Chem. 1964 Feb;239:375–380. [PubMed] [Google Scholar]
  24. Roach P. J., Goldman M. Modification of glycogen synthase activity in isolated rat hepatocytes by tumor-promoting phorbol esters: evidence for differential regulation of glycogen synthase and phosphorylase. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7170–7172. doi: 10.1073/pnas.80.23.7170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sariban-Sohraby S., Burg M., Wiesmann W. P., Chiang P. K., Johnson J. P. Methylation increases sodium transport into A6 apical membrane vesicles: possible mode of aldosterone action. Science. 1984 Aug 17;225(4663):745–746. doi: 10.1126/science.6463652. [DOI] [PubMed] [Google Scholar]
  26. Varela I., Mérida I., Pajares M., Villalba M., Mato J. M. Activation of partially purified rat liver lipid methyltransferase by phosphorylation. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1065–1070. doi: 10.1016/0006-291x(84)91199-9. [DOI] [PubMed] [Google Scholar]
  27. Varela I., Mérida I., Villalba M., Vivanco F., Mato J. M. Phospholipid methyltransferase phosphorylation by intact hepatocytes: effect of glucagon. Biochem Biophys Res Commun. 1985 Aug 30;131(1):477–483. doi: 10.1016/0006-291x(85)91827-3. [DOI] [PubMed] [Google Scholar]
  28. Villalba M., Pajares M. A., Renart M. F., Mato J. M. Protein kinase C catalyses the phosphorylation and activation of rat liver phospholipid methyltransferase. Biochem J. 1987 Feb 1;241(3):911–916. doi: 10.1042/bj2410911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WIELAND O. Eine enzymatische Methode zur Bestimmung von Glycerin. Biochem Z. 1957;329(4):313–319. [PubMed] [Google Scholar]
  30. Walkenbach R. J., Hazen R., Larner J. Reversible inhibition of cyclic AMP-dependent protein kinase by insulin. Mol Cell Biochem. 1978 Feb 24;19(1):31–41. doi: 10.1007/BF00231232. [DOI] [PubMed] [Google Scholar]
  31. van de Werve G., Proietto J., Jeanrenaud B. Tumour-promoting phorbol esters increase basal and inhibit insulin-stimulated lipogenesis in rat adipocytes without decreasing insulin binding. Biochem J. 1985 Jan 15;225(2):523–527. doi: 10.1042/bj2250523. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES