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Platelet-Activating Factor in Brain: Its Metabolism, Roles, and Involvement in Neurological Disorders

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Abstract

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent biologically active mediator that is involved in intracellular and extracellular communication. PAF belongs to a family of biologically active and structurally related alkyl phospholipids produced by neural and non-neural cells (neural cells, macrophages, platelets, endothelial cells, mast cells, and neutrophils). PAF not only induces platelet aggregation, but also enhances histamine and serotonin release resulting in vasodilation and enhancement in vascular permeability, increase in eosinophil and neutrophil motility, and degranulation producing edema, hyperemia, itching, and pain (Farooqui et al., 2008).

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References

  • Adachi T., Aoki J., Manya H., Asou H., Arai H., and Inoue K., (1997). PAF analogues capable of inhibiting PAF acetylhydrolase activity suppress migration of isolated rat cerebellar granule cells. Neurosci. Lett. 235:133–136.

    Article  PubMed  CAS  Google Scholar 

  • Aihara M., Ishii S., Kume K., and Shimizu T. (2000). Interaction between neurone and microglia mediated by platelet-activating factor. Genes Cells 5:397–406.

    Article  PubMed  CAS  Google Scholar 

  • Arai H. (2002). Platelet-activating factor acetylhydrolase. Prostaglandins Other Lipid Mediat. 68–69:83–94.

    Article  PubMed  Google Scholar 

  • Arai H., Koizumi H., Aoki J., and Inoue K. (2002). Platelet-activating factor acetylhydrolase (PAF-AH). J. Biochem. 131:635–640.

    PubMed  CAS  Google Scholar 

  • Baker P. R. S., Owen J. S., Nixon A. B., Thomas L. N., Wooten R., Daniel L. W., O’Flaherty J. T., and Wykle R. L. (2002). Regulation of platelet-activating factor synthesis in human neutrophils by MAP kinases. Biochim. Biophys. Acta Mol. Cell Res. 1592:175–184.

    CAS  Google Scholar 

  • Baker R. R. and Chang H. (1993). The potential for platelet-activating 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 Lipids Lipid Metab. 1170:157–164.

    Article  CAS  Google Scholar 

  • Baker R. R. and Chang H. (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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Baker R. R. and Chang H. Y. (2000). The regulation of CoA-independent transacylation reactions in neuronal nuclei by lysophospholipid, free fatty acid, and lysophospholipase: the control of nuclear lyso platelet-activating factor metabolism. Mol. Cell. Biochem. 215:135–144.

    Article  PubMed  CAS  Google Scholar 

  • Baker R. R. and Chang H. Y. (2002). MgATP may depress de novo neuronal nuclear PAF generation by promoting the formation of alkylacylglycerophosphate, an inhibitor of alkylglycerophosphate acetyltransferase. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1585:44–49.

    CAS  Google Scholar 

  • Bate C., Salmona, M. and Williams A. (2004). The role of platelet activating factor in prion and amyloid-beta neurotoxicity. Neuroreport. 15: 509–513.

    Article  PubMed  CAS  Google Scholar 

  • Bate C., Tayebi M., and Williams A. (2008). Ginkgolides protect against amyloid-beta1-42-mediated synapse damage in vitro. Mol. Neurodegener. 3:1.

    Article  PubMed  CAS  Google Scholar 

  • Bate C., Tayebi M., and Williams A. (2010). Phospholipase A2 inhibitors protect against prion and Abeta mediated synapse degeneration. Mol Neurodegener. 5:13.

    Article  PubMed  CAS  Google Scholar 

  • Bazan N. G., Squinto S. P., Braquet P., Panetta T., and Marcheselli V. L. (1991). Platelet-activating factor and polyunsaturated fatty acids in cerebral ischemia or convulsions: Intracellular PAF-binding sites and activation of a fos/jun/AP-1 transcriptional signaling system. Lipids 26:1236–1242.

    Article  PubMed  CAS  Google Scholar 

  • Bazan N. G., Fletcher B. S., Herschman H. R., and Mukherjee P. K. (1994). Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. Proc. Natl. Acad. Sci. USA 91:5252–5256.

    Article  PubMed  CAS  Google Scholar 

  • Bazan N. G. (2003). Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J. Lipid Res. 44:2221–2233.

    Article  PubMed  CAS  Google Scholar 

  • Belayev L., Khoutorova L., Atkins K., Cherqui A., Alvarez-Builla J., Bazan N.G. (2009). LAU-0901, a novel platelet-activating factor receptor antagonist, confers enduring neuroprotection in experimental focal cerebral ischemia in the rat. Brain Res. 1253:184–190.

    Article  PubMed  CAS  Google Scholar 

  • Bennett S.A., Chen J., Pappas B.A., Roberts D.C., and Tenniswood M. (1998). Platelet activating factor receptor expression is associated with neuronal apoptosis in an in vivo model of excitotoxicity. Cell Death Differ. 5: 867–875.

    Article  PubMed  CAS  Google Scholar 

  • Bito H., Nakamura M., Honda Z., Izumi T., Iwatsubo T., Seyama Y., Ogura A., Kudo Y., and Shimizu T. (1992). Platelet-activating factor (PAF) receptor in rat brain: PAF mobilizes intracellular Ca2+ in hippocampal neurons. Neuron 9:285–294.

    Article  PubMed  CAS  Google Scholar 

  • Blank M.L., Lee T., Fitzgerald V., and Snyder F. (1981). A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid). J. Biol. Chem. 256:175–178.

    PubMed  CAS  Google Scholar 

  • Blank M. L., Lee Y. J., Cress E. A., and Snyder F. (1988). Stimulation of the de novo pathway for the biosynthesis of platelet-activating factor (PAF) via cytidylyltransferase activation in cells with minimal endogenous PAF production. J. Biol. Chem. 263:5656–5661.

    PubMed  CAS  Google Scholar 

  • Bix G. J. and Clark G. D. (1998). Platelet-activating factor receptor stimulation disrupts neuronal migration In vitro. J. Neurosci. 18: 307–318.

    PubMed  CAS  Google Scholar 

  • Bussolati B., Rollino C., Mariano F., Quarello F., and Camussi G. (2000). IL-10 stimulates production of platelet-activating factor by monocytes of patients with active systemic lupus erythematosus (SLE). Clin Exp Immunol. 122: 471–476.

    Article  PubMed  CAS  Google Scholar 

  • Chao W. and Olson M. S. (1993). Platelet-activating factor: Receptors and signal transduction. Biochem. J. 292:617–629.

    PubMed  CAS  Google Scholar 

  • Carolan E. J., and Casale. T. B. (1990). Degree of platelet activating factor-induced neutrophil migration is dependent upon the molecular species. J. Immunol. 145:2561–2565.

    PubMed  CAS  Google Scholar 

  • Clark, G.D., Zorumski, C.F., McNeil, R.S., Happel, L.T., Ovella, T., McGuire, S., Bix, G.J., and Swann, J.W. (2000). Neuronal platelet-activating factor receptor signal transduction involves a pertussis toxin-sensitive G-protein. Neurochem. Res. 25: 603–611.

    Article  PubMed  CAS  Google Scholar 

  • Collado A. P., Latorre E., Fernández I., Aragonés A. D., and Catalán R. E. (2003). Endothelin-1 decreases ethanolamine plasmalogen levels and evokes PAF production in brain microvessels. Microvasc. Res. 66:197–203.

    Article  PubMed  CAS  Google Scholar 

  • DeCoster M. A., Mukherjee P. K., Davis R. J., and Bazan N. G. (1998). Platelet-activating factor is a downstream messenger of kainate-induced activation of mitogen-activated protein kinases in primary hippocampal neurons. J. Neurosci. Res. 53:297–303.

    Article  PubMed  CAS  Google Scholar 

  • Derewenda Z. S. and Derewenda U. (1998). The structure and function of platelet-activating factor acetylhydrolases. Cell Mol. Life Sci. 54:446–455.

    Article  PubMed  CAS  Google Scholar 

  • Edwards L.J., and Constantinescu C.S. (2009). Platelet activating factor/platelet activating factor receptor pathway as a potential therapeutic target in autoimmune diseases. Inflamm Allergy Drug Targets. 8:182–190.

    PubMed  CAS  Google Scholar 

  • Farooqui A. A. and Horrocks L. A. (2007). Glycerophospholipids in the Brain: Phospholipases A2 in Neurological Disorders, pp. 1–394. Springer, New York.

    Google Scholar 

  • Farooqui A. A. Farooqui T.,and Horrocks L. A. (2008a). Metabolism and Functions of Bioactive Ether Lipids in the Brain. Springer, New York.

    Book  Google Scholar 

  • Farooqui A.A., Ong W.Y., and Horrocks L.A. (2006). Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev. 58:591–620.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui A.A., Horrocks L.A., and Farooqui T. (2007). Modulation of inflammation in brain: a matter of fat. J. Neurochem. 101:577–599.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui A.A. (2010). Neurochemical Aspects of Neurotraumatic and Neurodegenerative diseases. Springer New York.

    Book  Google Scholar 

  • Feuerstein G.Z. (1996). Platelet-activating factor: a case for its role in CNS function and brain injury. J Lipid Mediat Cell Signal. 14: 109–114.

    Article  PubMed  CAS  Google Scholar 

  • Francescangeli E., Boila A., and Goracci G. (2000). Properties and regulation of microsomal PAF-synthesizing enzymes in rat brain cortex. Neurochem. Res. 25: 705–713.

    Article  PubMed  CAS  Google Scholar 

  • Gelb M.H., Min J.-H., Jain M.K. (2000). Do membrane-bound enzymes access their substrates from the membrane or aqueous phase: interfacial versus non-interfacial enzymes. Biochim. Biophy. Acta 1488: 20–27.

    CAS  Google Scholar 

  • Gimenez R. and Aguilar J. (2001). Cytidine (5 ‘) diphosphocholine-induced decrease in cerebral platelet activating factor is due to inactivation of its synthesizing enzyme cholinephosphotransferase in aged rats. Neurosci. Lett. 299: 209–212.

    Article  PubMed  CAS  Google Scholar 

  • Giral M, Balsa D, Ferrando R, Merlos M, Garcia-Rafanell J. (1996) Effects of UR-12633, a new antagonist of platelet-activating factor, in rodent models of endotoxic shock. Br J Pharmacol. 118:1223–1231.

    PubMed  CAS  Google Scholar 

  • Goracci G. and Francescangeli E. (1991). Properties of PAF-synthesizing phosphocholinetransferase and evidence for lysoPAF acetyltransferase activity in rat brain. Lipids 26: 986–991.

    Article  PubMed  CAS  Google Scholar 

  • Goracci G., Balestrieri M.L., and Nardicchi V. (2009). Metabolism and functions of platelet-activating Factor (PAF) in the nervous tissue in Handbook of Neurochemistry and Molecular Neurobiology, 3rd Edition, pp. 311–352, Springer Science  +  Media, LIC.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Ha S.W., and Lee C.S. (2010). Differential effect of platelet activating factor on 1-methyl-4-phenylpyridinium-induced cell death through regulation of apoptosis-related protein activation. Neurochem Int. 56:819–828.

    Article  PubMed  CAS  Google Scholar 

  • Hattori M., Arai H., and Inoue K. (1993). Purification and characterization of bovine brain platelet-activating factor acetylhydrolase. J. Biol. Chem. 268: 18748–18753.

    PubMed  CAS  Google Scholar 

  • Hattori M., Adachi H., Tsijimoto M., Arai H., Inoue K. (1994) Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase. Nature. 370: 216–218.

    Article  PubMed  CAS  Google Scholar 

  • Hattori K., Adachi H., Matsuzawa A., Yamamoto K., Tsujimoto M., Aoki J., Hattori M., Arai H., and Inoue K. (1996). cDNA cloning and expression of intracellular platelet-activating factor (PAF) acetylhydrolase II. Its homology with plasma PAF acetylhydrolase. J. Biol. Chem. 271:33032–33038.

    Article  PubMed  CAS  Google Scholar 

  • Heller R., Bussolino F., Ghigo D., Garbarino G., Pescarmona G., Till U., and Bosia A. (1991). Stimulation of platelet-activating factor synthesis in human endothelial cells by activation of the de novo pathway. Phorbol 12-myristate 13-acetate activates 1-alkyl-2-lyso-sn-glycero-3-phosphate:acetyl-CoA acetyltransferase and dithiothreitol-insensitive 1-alkyl-2-acetyl-sn-glycerol:CDP-choline cholinephosphotransferase. J. Biol. Chem. 266: 21358–21361.

    PubMed  CAS  Google Scholar 

  • Hirashima Y., Endo S., Ohmori T., Kato R., and Takaku A. (1994). Platelet-activating factor (PAF) concentration and PAF acetylhydrolase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage. J. Neurosurg. 80: 31–36.

    Article  PubMed  CAS  Google Scholar 

  • Hocke M., Richter L., Bosseckert H., and Eitner K. (1999). Platelet activating factor in stool from patients with ulcerative colitis and Crohn’s disease. Hepatogastroenterology. 46:2333–2337.

    PubMed  CAS  Google Scholar 

  • Honda Z., Nakamura M., Miki I., Minami M., Watanabe T., Shimizu T. (1991). Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung. Nature 349: 342–346.

    Article  PubMed  CAS  Google Scholar 

  • Honda Z., Ishii S., and Shimizu T. (2002). Platelet-activating factor receptor. J. Biochem. 131: 773–779.

    PubMed  CAS  Google Scholar 

  • Hostettler M.E., and Carlson S.L. (2002). PAF antagonist treatment reduces pro-inflammatory cytokine mRNA after spinal cord injury. Neuroreport. 13:21–24.

    Article  PubMed  CAS  Google Scholar 

  • Ishii S., Matsuda Y., Nakamura M., Waga I., Kume K., Izumi T., and Shimizu T. (1996). A murine platelet-activating factor receptor gene: cloning, chromosomal localization and up-regulation of expression by lipopolysaccharide in peritoneal resident macrophages. Biochem. J. 314: 671–678.

    PubMed  CAS  Google Scholar 

  • Ishii, I., Izumi, T., Tsukamoto, H., Umeyama, H., Ui, M., and Shimizu. T. (1997). Alanine exchanges of polar amino acids in the transmembrane domains of a platelet-activating factor receptor generate both constitutively active and inactive mutants. J. Biol. Chem. 272:7846–7854.

    Article  PubMed  CAS  Google Scholar 

  • Ishii S. and Shimizu T. (2000). Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog. Lipid Res. 39: 41–82.

    Article  PubMed  CAS  Google Scholar 

  • Izumi T. and Shimizu T. (1995). Platelet-activating factor receptor: Gene expression and signal transduction. Biochim. Biophys. Acta Lipids Lipid Metab. 1259: 317–333.

    Article  Google Scholar 

  • Karasawa K., Qiu X., and Lee T. (1999). Purification and characterization from rat kidney membranes of a novel platelet-activating factor (PAF)-dependent transacetylase that catalyzes the hydrolysis of PAF, formation of PAF analogs, and C2-ceramide. J. Biol. Chem. 274: 8655–8661.

    Article  PubMed  CAS  Google Scholar 

  • Karasawa K., Harada A., Satoh N., Inoue K., and Setaka M. (2003). Plasma platelet activating factor-acetylhydrolase (PAF-AH). Prog. Lipid Res. 42:93–114.

    Article  PubMed  CAS  Google Scholar 

  • Kasperska-Zajac A., Brzoza Z., and Rogala B. (2008). Platelet activating factor as a mediator and therapeutic approach in bronchial asthma. Inflammation 31:112–120.

    Article  PubMed  CAS  Google Scholar 

  • Kihara Y., Yanagida K., Masago K., Kita Y., Hishikawa D., Shindou H., Ishii S., and Shimizu T. (2008). Platelet-activating factor production in the spinal cord of experimental allergic encephalomyelitis mice via the group IVA cytosolic phospholipase A2-lyso-PAFAT axis. J Immunol. 181:5008–5014.

    PubMed  CAS  Google Scholar 

  • Kornecki E. and Ehrlich Y. H. (1991). Calcium ion mobilization in neuronal cells induced by PAF. Lipids 26:1243–1246.

    Article  PubMed  CAS  Google Scholar 

  • Kunievsky B., and Yavin E. (1994). Production and metabolism of platelet-activating factor in the normal and ischemic fetal rat brain. J. Neurochem. 63: 2144–2151.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Lee T. C., Malone B., Blank M. L., Fitzgerald V., and Snyder F. (1990). Regulation of the synthesis of platelet-activating factor and its inactive storage precursor (1-alkyl-2-acyl-sn-glycero-3-phosphocholine) from 1-alkyl-2-acetyl-sn-glycerol by rabbit platelets. J. Biol. Chem. 265: 9181–9187.

    PubMed  CAS  Google Scholar 

  • Lee T. C., Uemura Y., and Snyder F. (1992). A novel CoA-independent transacetylase produces the ethanolamine plasmalogen and acyl analogs of platelet-activating factor (PAF) with PAF as the acetate donor in HL-60 cells. J. Biol. Chem. 267:19992–20001.

    PubMed  CAS  Google Scholar 

  • Li, T., Southall M. D., Yi Q., Pei Y., Lewis D., Al-Hassani M., Spandau D., and Travers J. B. (2003). The epidermal platelet-activating factor receptor augments chemotherapy-induced apoptosis in human carcinoma cell lines. J. Biol. Chem. 278: 16614–16621.

    Article  PubMed  CAS  Google Scholar 

  • Lu J., Caplan M.S., Li D., and Jilling T. (2008). Polyunsaturated fatty acids block platelet-activating factor-induced phosphatidylinositol 3 kinase/Akt-mediated apoptosis in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 294:G1181-G1190.

    Article  PubMed  CAS  Google Scholar 

  • Lupia E., Del Sorbo L., Bergerone S., Emanuelli G., Camussi G., and Montrucchio G. (2003). The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils. Immunology. 109:557–563.

    Article  PubMed  CAS  Google Scholar 

  • Lynch, J.M.. and Hensen, P.M. (1986). The intracellular retention of newly synthesized platelet-activating factor. J Immunol. 137: 2653–2661.

    PubMed  CAS  Google Scholar 

  • Maclennan K. M., Smith P. F., and Darlington C. L. (1996). Platelet-activating factor in the CNS. Prog. Neurobiol. 50: 585–596.

    Article  PubMed  CAS  Google Scholar 

  • Manya H., Aoki J., Watanabe M., Adachi T., Asou H., Inoue Y., Arai H., and Inoue K. (1998). Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain. J. Biol. Chem. 273:18567–18572.

    Article  PubMed  CAS  Google Scholar 

  • Manya H., Aoki J., kato H., Ishii J., Hino S., Arai H., and Inoue K. (1999). Biochemical characterization of various catalytic complexes of the brain platelet-activating factor acetylhydrolase. J.Biol. Chem. 274: 31827–31832.

    Article  PubMed  CAS  Google Scholar 

  • Marcheselli V. L., Rossowska M. J., Domingo M. T., Braquet P., and Bazan N. G. (1990). Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. J. Biol. Chem. 265:9140–9145.

    PubMed  CAS  Google Scholar 

  • Margues S.A., Dy L.C., Southall M.D., Yi O., Smietana E., Kapur R., Margues M., Travers J.B. and Spandau D.F. (2002). The platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway. J. Pharmacol. Exp. Ther. 300: 1026–1035.

    Article  Google Scholar 

  • Mathiak G., Szewczyk D., Abdullah F., Ovadia P., and Rabinovici R. (1997). Platelet-activating factor (PAF) in experimental and clinical sepsis. Shock. 7:391–404.

    Article  PubMed  CAS  Google Scholar 

  • Mazer B.D., Sawami H., Franklin R., and Gelfand E.W. (1991). B-cell activation and regulation of immunoglobulin synthesis by platelet-activating factor. Neth. J. Med. 39: 244–253.

    PubMed  CAS  Google Scholar 

  • McHowat J., Kell P. J., O’Neill H. B., and Creer M. H. (2001). Endothelial cell PAF synthesis following thrombin stimulation utilizes Ca2+-independent phospholipase A2. Biochemistry 40: 14921–14931.

    Article  PubMed  CAS  Google Scholar 

  • McLamon J.G., Choi H.B., Lue L.F., Walker D.G., and Kim S.U. (2005). Perturbations in calcium-mediated signal transduction in microglia from Alzheimer’s disease patients. J. Neurosci. Res. 81:426–435.

    Article  CAS  Google Scholar 

  • McMullen T.W., Li J., Sheffield P.J., Aoki J., Martin T.W., Arai H., Inoue K., and Derewenda Z.S. (2000). The functional implications of the dimerization of the catalytic subunits of the mammalian brain platelet-activating factor acetylhydrolase (Ib). Protein Eng. 13: 865–871.

    Article  PubMed  CAS  Google Scholar 

  • Min J. H., Wilder C., Aoki J., Arai K., Inoue K., Paul L., and Gelb M. H. (2001). Platelet-activating factor acetylhydrolases: Broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme. Biochemistry 40:4539–4549.

    Article  PubMed  CAS  Google Scholar 

  • Mori M., Aihara M., Kume K., Hamanoue M., Kohsaka S., and Shimizu T. (1996). Localization of platelet-activating factor receptor in the rat brain. Adv. Exp. Med. Biol. 407:357–363: 357–363.

    Google Scholar 

  • Moriguchi S., Shioda N., Yamamoto Y., and Fukunaga K. (2010). Platelet-activating factor-induced synaptic facilitation is associated with increased calcium/calmodulin-dependent protein kinase II, protein kinase C and extracellular signal-regulated kinase activities in the rat hippocampal CA1 region. Neuroscience 166:1158–1168.

    Article  PubMed  CAS  Google Scholar 

  • Nixon A. B., O’Flaherty J. T., Salyer J. K., and Wykle 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.

    Article  PubMed  CAS  Google Scholar 

  • Noris M., Benigni A., Boccardo P., Gotti E., Benfenati E., Aiello S., Todeschini M., and Remuzzi G. (1993). Urinary excretion of platelet activating factor in patient with immune-mediated glomerulonephritis. Kidney Int. 43:426–429.

    Article  PubMed  CAS  Google Scholar 

  • O’Flaherty J. T., Tessner, T., Greene D., Redman J. R., and Wykle R. L. (1994). Comparison of 1-O-alkyl-, 1-O-alk-1’-enyl-, and 1-O-acyl-2-acetyl-sn- glycero-3-phosphoethanolamines and −3-phosphocholines as agonists of the platelet-activating factor family. Biochim. Biophys. Acta. 1210: 209–216.

    PubMed  Google Scholar 

  • Ottino P., He J., Axelrod T.W., Bazan H.E. (2005). PAF-induced furin and MT1-MMP expression is independent of MMP-2 activation in corneal myofibroblasts. Invest Ophthalmol Vis Sci. 46: 487–496.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Prescott S. M., Zimmerman G. A., and McIntyre T. M. (1990). Platelet-activating factor. J. Biol. Chem. 265: 17381–17384.

    PubMed  CAS  Google Scholar 

  • Prescott S. M., Zimmerman G. A., Stafforini D. M., and McIntyre T. M. (2000). Platelet-activating factor and related lipid mediators. Annu. Rev. Biochem. 69: 419–445.

    Article  PubMed  CAS  Google Scholar 

  • Ryan S.D., Harris C.S., Carswell C.L., Baenziger J.E., and Bennett S.A. (2008). Heterogeneity in the sn-1 carbon chain of platelet-activating factor glycerophospholipids determines pro- or anti-apoptotic signaling in primary neurons. J. Lipid Res. 49:2250–2258.

    Article  PubMed  CAS  Google Scholar 

  • Rehder V., Jensen J.R., and Kater S.B. (1992). The initial stages of neural regeneration are dependent upon intracellular calcium levels. Neuroscience. 51: 565–574.

    Article  PubMed  CAS  Google Scholar 

  • Rubin B. B., Downey G. P., Koh A., Degousee N., Ghomashchi F., Nallan L., Stefanski E., Harkin D. W., Sun C. X., Smart B. P., Lindsay T. F., Cherepanov V., Vachon E., Kelvin D., Sadilek M., Brown G. E., Yaffe M. B., Plumb J., Grinstein S., Glogauer M., and Gelb M. H. (2005). Cytosolic phospholipase A2-α is necessary for platelet-activating factor biosynthesis, efficient neutrophil-mediated bacterial killing, and the innate immune response to pulmonary infection - cPLA2-α.

    Google Scholar 

  • Sarchielli P., Alberti A., Coppola F., Baldi A., Gallai B., Floridi A., Floridi A., Capocchi G., and Gallai V. (2004). Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks. Cephalalgia. 24: 623–630.

    Article  PubMed  CAS  Google Scholar 

  • Shi C., Zhao L., Zhu B., Li Q., Yew D.T., Yao Z., and Xu J. (2009). Dosage effects of EGb761 on hydrogen peroxide-induced cell death in SH-SY5Y cells. Chem. Biol. Interact 180:389–397.

    Article  PubMed  CAS  Google Scholar 

  • Shindou H., Hishikawa D., Nakanishiu H., Harayama T., Ishii S., Taguchi R., and Shimizu T. (2007). A single enzyme catalyzes both platelet-activating factor production and membrane biogenesis of inflammatory cells - Cloning and characterization of acetyl-CoA:lyso-PAF acetyltransferase. J. Biol. Chem. 282: 6532–6539.

    Article  PubMed  CAS  Google Scholar 

  • Shmueli O., Cahana A., and Reiner O. (1999). Platelet-activating factor (PAF) acetylhydrolase activity, LIS1 expression, and seizures. J Neurosci Res. 57:176–184.

    Article  PubMed  CAS  Google Scholar 

  • Smiley P. L., Stremler K. E., Prescott S. M., Zimmerman G. A., and McIntyre T. M. (1991). Oxidatively fragmented phosphatidylcholines activate human neutrophils through the receptor for platelet-activating factor. J. Biol. Chem. 266: 11104–11110.

    PubMed  CAS  Google Scholar 

  • Smith C.S. and Shearer W.T. (1994). Activation of NF-kB and immunoglobulin expression in a human B cell line. Cell Immunol. 155:292–303.

    Article  PubMed  CAS  Google Scholar 

  • Snyder F. (1995). Platelet-activating factor: the biosynthetic and catabolic enzymes. Biochem. J. 305: 689–705.

    PubMed  CAS  Google Scholar 

  • Snyder F. (1997). CDP-choline:alkylacetylglycerol cholinephosphotransferase catalyzes the final step in the de novo synthesis of platelet-activating factor. Biochim. Biophys. Acta 1348: 111–116.

    PubMed  CAS  Google Scholar 

  • Snyder F., Fitzgerald V., and Blank M. L. (1996). Biosynthesis of platelet-activating factor and enzyme inhibitors. Adv. Exp. Med. Biol. 416: 5–10.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Stafforini D. M., McIntyre T. M., Carter M. E., and Prescott S. M. (1987). Human plasma platelet-activating factor acetylhydrolase Association with lipoprotein particles and role in the degradation of platelet-activating factor. J. Biol. Chem. 262: 4215–4222.

    PubMed  CAS  Google Scholar 

  • Stafforini D. M., Prescott S. M., Zimmerman G. A., and McIntyre T. M. (1996). Mammalian platelet-activating factor acetylhydrolases. Biochim. Biophys. Acta 1301: 161–173.

    PubMed  Google Scholar 

  • Stafforini D.M., McIntyre T.M., Zimmerman G.A., and Prescott S.M. (1997). Platelet-activating factor acetylhydrolases. J. Biol. Chem. 272: 17895–17898.

    Article  PubMed  CAS  Google Scholar 

  • Stafforini D.M., Sheller J.R., Blackwell T.S., Sapirstein A., Yull F.E., McIntyre T.M., Bonventre J.V., Prescott S.M., and Roberts L.J. 2nd. (2006). Release of free F2-isoprostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases. J Biol Chem. 281:4616–4623.

    Article  PubMed  CAS  Google Scholar 

  • Stafforini D.M. (2009). Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2. Cardiovasc. Drugs Ther. 23:73–83.

    Article  PubMed  CAS  Google Scholar 

  • Squinto S.P., Block A.L., Braquet P., and Bazan N.G. (1989). Platelet-activating factor stimulates a fos/jun/AP-1 transcriptional signaling system in human neuroblastoma cells. J Neurosci Res. 24:558–566.

    Article  PubMed  CAS  Google Scholar 

  • Tetta C., Bussolino F., Modena V., Montrucchio G., Segoloni G., Pescarmona G., and Camussi G. (1990). Release of platelet-activating factor in systemic lupus erythematosus. Int Arch Allergy Appl Immunol. 91:244–256.

    Article  PubMed  CAS  Google Scholar 

  • Tjoelker L. W. and Stafforini D. M. (2000). Platelet-activating factor acetylhydrolases in health and disease. Biochim. Biophys. Acta 1488:102–123.

    PubMed  CAS  Google Scholar 

  • Tokutomi T., Maruiwa H., Hirohata M., Miyagi T., and Shigemori M. (2001). Production of platelet-activating factor by neuronal cells in the rat brain with cold injury. Neurol Res. 23:605–611.

    Article  PubMed  CAS  Google Scholar 

  • Tosaki T., Sakamoto H., Kitahara J., Imai H., and Nakagawa Y. (2007). Enhancement of acetyl-CoA: 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity by hydrogen peroxide. Biol. Pharm. Bull. 30: 272–278.

    Article  PubMed  CAS  Google Scholar 

  • Townsend G.C., and Scheld W.M. (1994). Platelet-activating factor augments meningeal inflammation elicited by Haemophilus influenzae lipooligosaccharide in an animal model of meningitis. Infect Immun. 62:3739–3744.

    PubMed  CAS  Google Scholar 

  • Tselepis A.D., Elisaf M., Besis S., Karabina S.A., Chapman M.J., and Siamopoulou A. (1999). Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity. Arthritis. Rheum. 42: 373–383.

    Article  PubMed  CAS  Google Scholar 

  • Tselepis A. D. and Chapman M. J. (2002). Inflammation, bioactive lipids and atherosclerosis: potential roles of a lipoprotein-associated phospholipase A2, platelet activating factor-acetylhydrolase. Atherosclerosis Suppl. 3: 57–68.

    Article  CAS  Google Scholar 

  • Tsoupras A.B., Chini M., Tsogas N., Fragopoulou E., Nomikos T., Lioni A., Mangafas N., Demopoulos C.A., Antonopoulou S., and Lazanas M.C. (2008). Anti-platelet-activating factor effects of highly active antiretroviral therapy (HAART): a new insight in the drug therapy of HIV infection? AIDS Res Hum Retroviruses. 24:1079–1086.

    Article  PubMed  CAS  Google Scholar 

  • Tsukioka K., Matsuzaki M., Nakamata M., Kayahara H., and Nakagawa T. (1996). Increased plasma level of platelet-activating factor (PAF) and decreased serum PAF acetylhydrolase (PAFAH) activity in adults with bronchial asthma. J. Investig. Allergol. Clin. Immunol. 6:22–29.

    PubMed  CAS  Google Scholar 

  • Umemura K., Kato I., Hirashima Y., Ishii Y., Inoue T., Aoki J., Kono N., Oya T., Hayashi N., Hamada H., Endo S., Oda M., Arai H., Kinouchi H., and Hiraga K. (2007). Neuroprotective role of transgenic PAF-acetylhydrolase II in mouse models of focal cerebral ischemia. Stroke 38:1063–1068.

    Article  PubMed  CAS  Google Scholar 

  • Vallari D. S., Record M., and Snyder F. (1990). Conversion of alkylacetylglycerol to platelet-activating factor in HL-60 cells and subcellular localization of the mediator. Arch. Biochem. Biophys. 276: 538–545.

    Article  PubMed  CAS  Google Scholar 

  • Vallee R.B., Faulkner N.E., and Tai C.Y. (2000). The role of cytoplasmic dynein in the human brain developmental disease lissencephaly. Biochim. Biophys. Acta 1496:89–98.

    Article  PubMed  CAS  Google Scholar 

  • Walsh C.A. (1998). LISsen up! Nature Genet. 19:307–308.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, 43210, USA

    Akhlaq A. Farooqui

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Farooqui, A.A. (2011). Platelet-Activating Factor in Brain: Its Metabolism, Roles, and Involvement in Neurological Disorders. In: Lipid Mediators and Their Metabolism in the Brain. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9940-5_4

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