Skip to main content
Log in

Properties and Regulation of Microsomal PAF-Synthesizing Enzymes in Rat Brain Cortex

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Platelet-activating factor (PAF) is a phospholipid mediator of long-term potentiation, synaptic plasticity and memory formation as well as of the development of brain damage. In brain, PAF is synthesized by two distinct pathways but their relative contribution to its productions, in various physiological and pathological conditions, is not established. We have further investigated on the properties of the two enzymes that catalyze the last step of the de novo or remodeling pathways in rat brain microsomes, PAF-synthesizing phosphocholinetransferase (PAF-PCT) and lysoPAF acetyltransferase (lysoPAF-AT), respectively. The latter enzyme is fully active at μM Ca2+ concentration, inhibited by MgATP and activated by phosphorylation. Because the reversibility of the reaction catalyzed by PAF-PCT, its direction depends on the ratio [CDP-choline]/[CMP] which is related to the energy charge of the cell. These and other properties indicate that the de novo pathway should mainly contribute to PAF synthesis for maintaining its basal levels under physiological conditions. The remodeling pathway should be more involved in the production of PAF during ischemia. During reperfusion, the overproduction of PAF should be the result of the concomitant activation of both pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Goracci, G. 1990. PAF in the nervous system: biochemistry and pathophysiology. Pages 377-388, in Kriaglstein, J. and Oberpichler, H. (eds.), Pharmacology of Cerebral Ischemia, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart.

    Google Scholar 

  2. Baker, R. R. 1995. Enzymes of platelet activating factor synthesis in brain. Neurochem. Res. 20:1345-1351.

    Google Scholar 

  3. Bazan, N. G. 1998. The neuromessenger platelet-activating factor in plasticity and neurodegeneration. Progress in Brain Research 118:281-291.

    Google Scholar 

  4. Bussolino, F., Gremo, F., Tetra, C., Pescarmona, G. P., and Camussi, G. 1986. Production of platelet-activating factor by chick retina. J. Biol. Chem. 261:16502-16508.

    Google Scholar 

  5. Sogos, V., Bussolino, F., Pilia, E., Torelli, S., and Gremo, F. 1990. Acetylcholine-induced production of platelet-activating factor by human fetal brain cells in culture. J. Neurosci. Res. 27: 706-711.

    Google Scholar 

  6. Nogami, K., Hirashima, Y., Endo, S., and Takaku, A. 1997. Involvement of platelet-activating factor (PAF) in glutamate neurotoxicity in rat neuronal cultures. Brain Res. 754:72-78.

    Google Scholar 

  7. Bussolino, F., Tessari, F., Turrini, F., Braquet, P., Camussi, G., Prosdocimi, M., and Bosia, A. 1988. Platelet activating factor induces dopamine release in PC-12 cell line. American Journal of Physiology 255:C559-C565.

    Google Scholar 

  8. Clark, G. D., Happel, L. T., Zorumski, C. F., and Bazan, N. G. 1992. Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 9:1211-1216.

    Google Scholar 

  9. Kato, K., Clark, G. D., Bazan, N. G., and Zorumski, C. F. 1994. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature 367:175-179.

    Google Scholar 

  10. Wieraszko, A., Gang, L., Kornecki, E., Hogan, M. V., and Ehrlich, Y. H. 1993. Long-term potentiation in the hippocampus induced by platelet-activating factor. Neuron 10:553-557.

    Google Scholar 

  11. Grassi, S., Francescangeli, E., Goracci, G., and Pettorossi, V. E. 1998. Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei. J. Neurophysiol. 79: 3266-3271.

    Google Scholar 

  12. Grassi, S., Francescangeli, E., Goracci, G., and Pettorossi, V. E. 1999. Platelet-activating factor and group I metabotropic glutamate receptors interact for full development and maintenance of long-term potentiation in the rat medial vestibular nuclei. Neuroscience 94:549-559.

    Google Scholar 

  13. Domingo, M. T., Spinnewyn, B., Chabrier, P. E., and Braquet, P. 1988. Presence of specific binding sites for platelet-activating factor (PAF) in brain. Biochem. Biophys. Res. Commun. 151: 730-736.

    Google Scholar 

  14. Bito, H., Honda, Z., Nakamura, M., and Shimizu, T. 1994. Cloning, expression and tissue distribution of rat platelet-activating-factor-receptor cDNA. Eur. J. Biochem. 221:211-218.

    Google Scholar 

  15. Kornecki, E. and Ehrlich, Y. H. 1988. Neuroregulatory and neuropathological actions of the ether-phospholipid plateletactivating factor. Science 240:1792-1794.

    Google Scholar 

  16. Francescangeli, E., Lang, D., Dreyfus, H., Boila, A., Freysz, L., and Goracci, G. 1977. Activities of enzymes involved in the metabolism of platelet-activating factor in neural cell cultures during proliferation and differentiation. Neurochem. Res. 22: 1299-1307.

    Google Scholar 

  17. Albrecht, U., Abu-Issa, R., Ratz, B., Hattori, M., Aoki, J., Arai, H., Inoue, K. and Eichele, G. 1996. Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuronal migration and platelet-activating factor. Dev. Biol. 180:579-593.

    Google Scholar 

  18. Kumar, R., Harvey, S. A., Kester, M., Hanahan, D. J., and Olson, M. S. 1988. Production and effects of platelet-activating factor in the rat brain. Biochim. Biophys. Acta 963:375-383.

    Google Scholar 

  19. Domingo, M. T., Spinnewyn, B., Chabrier, P. E., and Braquet, P. 1994. Changes in [3H]PAF binding and PAF concentrations in gerbil brain after bilateral common carotid artery occlusion: a quantitative autoradiographic study. Brain Res. 640:268-276.

    Google Scholar 

  20. Nishida, K. and Markey, S. P. 1996. Platelet-activating factor in brain regions after transient ischemia in gerbils. Stroke 27:514-518.

    Google Scholar 

  21. Birkle, D. L., Kurian, P., Braquet, P., and Bazan, N. G. 1988. Platelet-activating factor antagonist BN52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock. J. Neurochem. 51: 1900-1905.

    Google Scholar 

  22. Panetta, T., Marcheselli, V. L., Braquet, P., Spinnewyn, B., and Bazan, N. G. 1987. Effects of a platelet activating factor antagonist (BN 52021) on free fatty acids, diacylglycerols, polyphosphoinositides and blood flow in the gerbil brain: inhibition of ischemia-reperfusion induced cerebral injury. Biochem. Biophys. Res. Commun. 149:580-587.

    Google Scholar 

  23. Kornecki, E. and Ehrlich, Y. H. 1991. Calcium Ion Mobilization in Neuronal cells Induced by PAF. Lipids 26:1243-1246.

    Google Scholar 

  24. Mukherjee, P. K., Decoster, M. A., Campbell, F. Z., Davis, R. J., and Bazan, N. G. 1999. Glutamate receptor signaling interplay modulates stress-sensitive mitogen-activated protein kinases and neuronal cell death. J. Biol. Chem. 274:6493-6498.

    Google Scholar 

  25. Perry, S. W., Hamilton, J. A., Tjoelker, L. W., Dbaibo, G., Dzenko, K. A., Epstein, L. G., Hannun, Y., Whittaker, J. S., Dewhurst, S., and Gelbard, H. A. 1998. Platelet-activating factor receptor activation-An initiator step in HIV-1 neuropathogenesis. J. Biol. Chem. 273:17660-17664.

    Google Scholar 

  26. Nishida, K., Markey, S. P., Kustova, Y., Morse, H. C., Skolnick, P., Basile, A. S., and Sei, Y. 1996. Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated. J. Neurochem. 66: 433-435.

    Google Scholar 

  27. Hershkowitz, M. and Adunsky, A. 1996. Binding of plateletactivating factor to platelets of Alzheimer' disease and multiinfarct dementia patients. Neurobiology of Aging 17:865-868.

    Google Scholar 

  28. Callea, L., Arese, M., Orlandini, A., Bargnani, C., Priori, A., and Bussolino, F. 1999. Platelet activating factor is elevated in cerebral spinal fluid and plasma of patients with relapsingremitting multiple sclerosis. J. Neuroimmunol. 94:212-221.

    Google Scholar 

  29. Lee, T. C., Malone, B., and Snyder, F. 1986. A new de novo pathway for the formation of 1-alkyl-2-acetyl-sn-glycerols, precursors of platelet activating factor. Biochemical characterization of 1-alkyl-2-lyso-sn-glycero-3-P: acetyl-CoA acetyltransferase in rat spleen. J. Biol. Chem. 261:5373-5377.

    Google Scholar 

  30. Baker, R. R. and Chang, H. Y. 1993. The potential for plateletactivating factor synthesis in brain: properties of cholinephosphotransferase and 1-alkyl-sn-glycero-3-phosphate acetyltransferase in microsomal fractions of immature rabbit cerebral cortex. Biochim. Biophys. Acta 1170:157-164.

    Google Scholar 

  31. Lee, T. C., Malone, B., and Snyder, F. 1988. Formation of 1-alkyl-2-acetyl-sn-glycerols via the de novo biosynthetic pathway for platelet-activating factor. Characterization of 1-alkyl-2-acetyl-sn-glycero-3-phosphate phosphohydrolase in rat spleens. J. Biol. Chem. 263:1755-1760.

    Google Scholar 

  32. Francescangeli, E. and Goracci, G. 1989. The de novo biosynthesis of platelet-activating factor in rat brain. Biochem. Biophys. Res. Comm. 161:107-112.

    Google Scholar 

  33. Goracci, G. and Francescangeli, E. 1991. Properties of PAFsynthesizing phosphocholinetransferase and evidence for lysoPAF acetyltransferase activity in rat brain. Lipids 26:986-991.

    Google Scholar 

  34. Woelk, H., Goracci, G., and Porcellati, G. 1974. The action of brain phospholipases A2 on purified, specifically labelled 1,2-diacyl-, 2-acyl-1-alk-1 '-enyl-and 2-acyl-1-alkyl-sn-glycero-3-phosphorylcholine. Hoppe-Seylers Zeitschrift fur Physiologische Chemie 355:75-81.

    Google Scholar 

  35. Rordorf, J., Uemura, Y., and Bonventre, J. V. 1991. Characterization of phospholipase A2 (PLA2) activity in gerbil brain: enhanced activities of cytosolic, mitochondrial, and microsomal forms after ischemia and reperfusion. J. Neurosci. 11:1829-1836.

    Google Scholar 

  36. Blank, M. L., Smith, Z. L., Fitzgerald, V., and Snyder, F. 1995. The CoA-independent transacylase in PAF biosynthesis: tissue distribution and molecular species selectivity. Biochim. Biophys. Acta 1254:295-301.

    Google Scholar 

  37. Baker, R. R. and Chang, H. Y. 1996. Alkylglycerophosphate acetyltransferase and lyso platelet activating factor acetyltransferase, two key enzymes in the synthesis of platelet activating factor, are found in neuronal nuclei isolated from cerebral cortex. Biochim. Biophys. Acta. 1302:257-263.

    Google Scholar 

  38. Lenihan, D. J. and Lee, T. C. 1984. Regulation of platelet activating factor synthesis: modulation of 1-alkyl-2-lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase by phosphorylation and dephosphorylation in rat spleen microsomes. Biochem. Biophys. Res. Commun. 120:834-839.

    Google Scholar 

  39. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, P. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem 193:265-275.

    Google Scholar 

  40. Goracci, G., Francescangeli, E., Horrocks, L. A., and Porcellati, G. 1983. The effect of CMP on the release of free fatty acids of rat brain in vitro. Neurochem. Res. 8:971-981.

    Google Scholar 

  41. Baker, R. R. and Chang, H. Y. 1998. MgATP has different inhibitory effects on the use of 1-acyl-lysophosphatidylcholine and lyso platelet-activating factor acceptors by neuronal nuclear acetyltransferase activities. Biochim. Biophys. Acta 1392:351-360.

    Google Scholar 

  42. Baker, R. R. and Chang, H. Y. 1998. Substrate specificities of neuronal nuclear acetyltransferases involved in the synthesis of platelet-activating factor. Differences in the use of 1-alkyl and 1-acyl lysophospholipid acceptors. Biochim. Biophys. Acta 1390:215-224.

    Google Scholar 

  43. Naraba, H., Ueno, A., Matsumoto, H., and Ohishi, S. 1996. Inhibitory effect of arachidonic acid on platelet-activating factor production in rat neutrophils. Eur. J. Pharmacol. 302:117-121.

    Google Scholar 

  44. Remy, E., Lenoir, G., Houben, A., Vandesteene, C., and Remacle, J. 1989. Inhibition of platelet-activating factor biosynthesis via the acetyltransferase by arachidonic and oleic acids in ionophore A23187-stimulated bovine neutrophils. Biochim. Biophys. Acta 1005:87-92.

    Google Scholar 

  45. Goracci, G., Francescangeli, E., Horrocks, L. A., and Porcellati, G. 1981. The reverse reaction of cholinephosphotransferase in rat brain microsomes. A new pathway for degradation of phosphatidylcholine. Biochim. Biophys. Acta 664:373-379.

    Google Scholar 

  46. Onodera, H., Iijima, K., and Kogure, K. 1986. Mononucleotide metabolism in the rat brain after transient ischemia. J. Neurochem. 46:1704-1710.

    Google Scholar 

  47. Baker, R. R. and Chang, H. Y. 1994. MgATP inhibits the synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphate by microsomal acetyltransferase of immature rabbit cerebral cortex. Biochim Biophys. Acta 1213:27-33.

    Google Scholar 

  48. Baker, R. R. and Chang, H. Y. 1995. Fatty acyl-CoA inhibits 1-alkyl-sn-glycero-3-phosphate acetyltransferase in microsomes of immature rabbit cerebral cortex: Control of the first committed step in the de novo pathway of platelet-activating factor synthesis. J. Neurochem. 64:364-370.

    Google Scholar 

  49. Stoll, L. L., Yerram, N. R., and Spector, A. A. 1991. Effect of differentiation on platelet-activating factor metabolism in HL-60 cells. J. Cell Sci. 100:145-152.

    Google Scholar 

  50. Farooqui, A. A., Yang, H. C., Rosenberger, T. A., and Horrocks, L. A. 1997. Phospholipase A2 and its role in brain tissue. J. Neurochem. 69:889-901.

    Google Scholar 

  51. Farooqui, A. A. and Horrocks, L. A. 1998. Plasmalogen-selective phospholipase A2 and its involvement in Alzheimer' disease. Biochemical Society Transactions 26:243-246.

    Google Scholar 

  52. Saluja, I., Song, D., Oregan, M. H., and Phillis, J. W. 1997. Role of phospholipase A2 in the release of free fatty acids during ischemia-reperfusion in the rat cerebral cortex. Neurosci. Lett. 233:97-100.

    Google Scholar 

  53. Francescangeli, E., Domanska-Janik, K., and Goracci, G. 1996. Relative contribution of the de novo and remodeling pathways to the synthesis of platelet-activating factor in brain areas and during ischemia. J. Lipid Med. & Cell Signalling 14:89-98.

    Google Scholar 

  54. Domenech, C., Machado-De Domenech, E., Soling, H-D. 1987. Regulation of acetyl-CoA: 1-alkyl-sn-glycero-3-phosphocholineacetyltransferase (lysoPAF-acetyltransferase) in exocrine glands. Evidence for an activation via phosphorylation by calcium/ calmodulin-dependent protein kinase. J. Biol. Chem. 262:5671-5676.

    Google Scholar 

  55. Nieto, M. L., Velasco, S., and Sanchez-Crespo, M. 1988. Modulation of acetyl-CoA:1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lysoPAF) acetyltransferase in human polymorphonuclears. The role of cyclic AMP-dependent and phospholipid sensitive, calcium-dependent protein kinases. J. Biol. Chem. 263: 4607-4611.

    Google Scholar 

  56. Hayashi, M., Imai, Y., and Oh-ishi, S. 1991. Phorbol ester stimulates PAF synthesis via the activation of protein kinase C in rat leukocytes. Lipids 26:1054-1059.

    Google Scholar 

  57. Nixon, A. B., O'Flaherty, J. T., Salyer, J. K., and Wylde, R. L. 1999. Acetyl-CoA:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase is directly activated by p38 kinase. J. Biol. Chem. 274:5469-5473

    Google Scholar 

  58. Francescangeli, E., Porcellati, S., and Goracci, G. 1997. CMP-dependent degradation of Platelet-activating factor (PAF) by rat brain microsomes. Pages 1029-1034 in Telken, A. W., and Koff, J. (eds.), Neurochemistry, Plenum Press.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Francescangeli, E., Boila, A. & Goracci, G. Properties and Regulation of Microsomal PAF-Synthesizing Enzymes in Rat Brain Cortex. Neurochem Res 25, 705–713 (2000). https://doi.org/10.1023/A:1007523422825

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007523422825

Navigation