Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Oct;121(1):79–87.

The effects of 1-oleoyl-2-acetylglycerol on platelet protein phosphorylation and platelet ultrastructure.

L L Friesen, J M Gerrard
PMCID: PMC1888023  PMID: 4050978

Abstract

1-oleoyl-2-acetylglycerol (OAG), an activator of protein kinase C and a synthetic diglyceride, was used in an investigation of the role of diglycerides in platelet stimulus-activation coupling. OAG (20-100 micrograms/ml) added to platelets resulted in rapid phosphorylation of the 47,000-dalton protein as well as a gradual dose dependent disappearance of alpha granules and dense bodies and the appearance of vacuolar structures containing remnants of granule matrix material. These morphologic changes occurred more slowly than the phosphorylation of 47K, which suggests that if these are related the phosphorylated 47K serves to activate some other mechanism, which is ultimately responsible for the changes observed. These results are most consistent with the role for the phosphorylation of 47K to promote granule labilization. Myosin light chain (MLC) phosphorylation also occurred. An absence of granule centralization suggests that MLC phosphorylation by protein kinase C may not trigger effective actin-myosin contraction.

Full text

PDF
83

Images in this article

Selected References

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

  1. Carroll R. C., Butler R. G., Morris P. A., Gerrard J. M. Separable assembly of platelet pseudopodal and contractile cytoskeletons. Cell. 1982 Sep;30(2):385–393. doi: 10.1016/0092-8674(82)90236-7. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Dabrowska R., Hartshorne D. J. A Ca2+-and modulator-dependent myosin light chain kinase from non-muscle cells. Biochem Biophys Res Commun. 1978 Dec 29;85(4):1352–1359. doi: 10.1016/0006-291x(78)91152-x. [DOI] [PubMed] [Google Scholar]
  4. Daniel J. L., Molish I. R., Rigmaiden M., Stewart G. Evidence for a role of myosin phosphorylation in the initiation of the platelet shape change response. J Biol Chem. 1984 Aug 10;259(15):9826–9831. [PubMed] [Google Scholar]
  5. Estensen R. D., White J. G. Ultrastructural features on the platelet response to phorbol myristate acetate. Am J Pathol. 1974 Mar;74(3):441–452. [PMC free article] [PubMed] [Google Scholar]
  6. Gerrard J. M., Townsend D., Stoddard S., Witkop C. J., White J. G. The influence of prostaglandin G2 on platelet ultrastructure and platelet secretion. Am J Pathol. 1977 Jan;86(1):99–116. [PMC free article] [PubMed] [Google Scholar]
  7. Ginsberg M. H., Taylor L., Painter R. G. The mechanism of thrombin-induced platelet factor 4 secretion. Blood. 1980 Apr;55(4):661–668. [PubMed] [Google Scholar]
  8. Haslam R. J., Lynham J. A. Relationship between phosphorylation of blood platelet proteins and secretion of platelet granule constituents. I. Effects of different aggregating agents. Biochem Biophys Res Commun. 1977 Jul 25;77(2):714–722. doi: 10.1016/s0006-291x(77)80037-5. [DOI] [PubMed] [Google Scholar]
  9. Hathaway D. R., Adelstein R. S. Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1653–1657. doi: 10.1073/pnas.76.4.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaibuchi K., Takai Y., Sawamura M., Hoshijima M., Fujikura T., Nishizuka Y. Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J Biol Chem. 1983 Jun 10;258(11):6701–6704. [PubMed] [Google Scholar]
  11. Kawahara Y., Takai Y., Minakuchi R., Sano K., Nishizuka Y. Phospholipid turnover as a possible transmembrane signal for protein phosphorylation during human platelet activation by thrombin. Biochem Biophys Res Commun. 1980 Nov 17;97(1):309–317. doi: 10.1016/s0006-291x(80)80169-0. [DOI] [PubMed] [Google Scholar]
  12. Kawahara Y., Takai Y., Minakuchi R., Sano K., Nishizuka Y. Possible involvement of Ca2+-activated, phospholipid-dependent protein kinase in platelet activation. J Biochem. 1980 Sep;88(3):913–916. doi: 10.1093/oxfordjournals.jbchem.a133048. [DOI] [PubMed] [Google Scholar]
  13. Kishimoto A., Takai Y., Mori T., Kikkawa U., Nishizuka Y. Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover. J Biol Chem. 1980 Mar 25;255(6):2273–2276. [PubMed] [Google Scholar]
  14. Lapetina E. G., Cuatrecasas P. Stimulation of phosphatidic acid production in platelets precedes the formation of arachidonate and parallels the release of serotonin. Biochim Biophys Acta. 1979 May 25;573(2):394–402. doi: 10.1016/0005-2760(79)90072-9. [DOI] [PubMed] [Google Scholar]
  15. Naka M., Nishikawa M., Adelstein R. S., Hidaka H. Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains. Nature. 1983 Dec 1;306(5942):490–492. doi: 10.1038/306490a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  18. Pollard H. B., Tack-Goldman K., Pazoles C. J., Creutz C. E., Shulman N. R. Evidence for control of serotonin secretion from human platelets by hydroxyl ion transport and osmotic lysis. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5295–5299. doi: 10.1073/pnas.74.12.5295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rink T. J., Sanchez A., Hallam T. J. Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets. Nature. 1983 Sep 22;305(5932):317–319. doi: 10.1038/305317a0. [DOI] [PubMed] [Google Scholar]
  20. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sano K., Takai Y., Yamanishi J., Nishizuka Y. A role of calcium-activated phospholipid-dependent protein kinase in human platelet activation. Comparison of thrombin and collagen actions. J Biol Chem. 1983 Feb 10;258(3):2010–2013. [PubMed] [Google Scholar]
  22. Takai Y., Kaibuchi K., Matsubara T., Nishizuka Y. Inhibitory action of guanosine 3', 5'-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets. Biochem Biophys Res Commun. 1981 Jul 16;101(1):61–67. doi: 10.1016/s0006-291x(81)80010-1. [DOI] [PubMed] [Google Scholar]
  23. Takai Y., Kishimoto A., Kikkawa U., Mori T., Nishizuka Y. Unsaturated diacylglycerol as a possible messenger for the activation of calcium-activated, phospholipid-dependent protein kinase system. Biochem Biophys Res Commun. 1979 Dec 28;91(4):1218–1224. doi: 10.1016/0006-291x(79)91197-5. [DOI] [PubMed] [Google Scholar]
  24. White J. G. Electron microscopic studies of platelet secretion. Prog Hemost Thromb. 1974;2(0):49–98. [PubMed] [Google Scholar]
  25. White J. G., Gerrard J. M. Interaction of microtubules and microfilaments in platelet contractile physiology. Methods Achiev Exp Pathol. 1979;9:1–39. [PubMed] [Google Scholar]
  26. White J. G., Rao G. H., Estensen R. D. Investigation of the release reaction in platelets exposed to phorbol myristate acetate. Am J Pathol. 1974 May;75(2):301–314. [PMC free article] [PubMed] [Google Scholar]
  27. Yamanishi J., Takai Y., Kaibuchi K., Sano K., Castagna M., Nishizuka Y. Synergistic functions of phorbol ester and calcium in serotonin release from human platelets. Biochem Biophys Res Commun. 1983 Apr 29;112(2):778–786. doi: 10.1016/0006-291x(83)91529-2. [DOI] [PubMed] [Google Scholar]
  28. Zucker M. B., Troll W., Belman S. The tumor-promoter phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate), a potent aggregating agent for blood platelets. J Cell Biol. 1974 Feb;60(2):325–336. doi: 10.1083/jcb.60.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES