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Degradation of Platelet-Activating Factor in Brain

Platelet-activating factor (PAF), a phospholipid mediator of inflammation, is rapidly synthesized by neural (neurons and glial cells) and nonneural cells in response to neurotransmitters (glutamate and its analogs), cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1), and pathological situations (Sogos et al., 1990; Prescott et al., 2000; Karasawa et al., 2003; Kunievsky and Yavin, 1994). PAF is normally present in the mammalian tissues in picomolar concentrations, and is found both in the cytosol and body fluids including blood plasma, cerebrospinal fluid, urine, and amniotic fluid (Lynch and Hensen, 1986; Cox et al., 1981; Billah et al., 1983). PAF is not stored in cells. Its levels in brain, other body tissues, and plasma are modulated by PAF-acetyl hydrolases. This enzyme inactivates PAF by removing the acetyl group from the sn-2 position of glycerol moiety and generating lyso-PAF, which is biologically inactive (Fig. 8.1). The lyso-PAF can be reacylated by an acyl-CoA/1-radyl-sn-glycero-3-phosphocholine acyltransferase. Alkyl-PAF is less potent than PAF. The alkyl moiety of lyso-PAF is degraded to an aldehyde by a tetrahydropiridine-dependent alkyl monooxygenase (Lee et al., 1981). Alternatively, a lysophospholipase D (lyso-PLD) can hydrolyze phosphocholine moiety to generate an analog of phosphatidic acid, or catalyze a phosphate transfer by a transphosphatidylation reaction (Wykle and Schremmer, 1974).

Keywords

Catalytic Subunit High Density Lipoprotein Serine Esterase Factor Acetylhydrolase Intracellular Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adachi T., Aoki J., Manya H., Asai 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.PubMedCrossRefGoogle Scholar
  2. Arai A. and Lynch G. (1992). Antagonists of the platelet-activating factor receptor block long-term potentiation in hippocampal slices. Eur. J. Neurosci. 4:411–419.PubMedCrossRefGoogle Scholar
  3. Arai H. (2002). Platelet-activating factor acetylhydrolase. Prostaglandins Other Lipid Mediat. 6869:83–94.CrossRefGoogle Scholar
  4. Arai H., Koizumi H., Aoki J., and Inoue K. (2002). Platelet-activating factor acetylhydrolase (PAF-AH). J. Biochem. 131:635–640.PubMedGoogle Scholar
  5. Baker R. R. (1995). Enzymes of platelet activating factor synthesis in brain. Neurochem. Res. 20:1345–1351.PubMedCrossRefGoogle Scholar
  6. Baker R. R. (2002). Lipid acetylation reactions and the metabolism of platelet-activating factor. Neurochem. Res. 25:677–683.Google Scholar
  7. Bate C., Salmona M. and Williams A. (2004). The role of platelet activating factor in prion and amyloid-beta neurotoxicity. Neuroreport. 15:509–513.PubMedCrossRefGoogle Scholar
  8. Bazan N. G. (2003). Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J. Lipid Res. 44:2221–2233.PubMedCrossRefGoogle Scholar
  9. Billah M. M. and Johnston J. M. (1983). Identification of phospholipid platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in human amniotic fluid and urine. Biochem. Biophys. Res. Commun. 113:51–58.PubMedCrossRefGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. Bonin F., Ryan S. D., Migahed L., Mo F., Lallier J., Franks D. J., Arai H., and Bennett S. A. L. (2004). Anti-apoptotic actions of the platelet-activating factor acetylhydrolase I α2 catalytic subunit. J. Biol. Chem. 279:52425–52436.PubMedCrossRefGoogle Scholar
  12. Contador M., Moya F. R., Zhao B., Furukawa M., Frenkel R. A., Guzzetta P., and Johnston J. M. (1997). Effect of dexamethasone on rat plasma platelet activating factor acetylhydrolase during the perinatal period. Early Hum. Dev. 47:167–176.PubMedCrossRefGoogle Scholar
  13. Cox C. P., Wardlow M. C., Jorgensen R., and Farr R. S. (1981). The presence of platelet-activating factor (PAF) in normal human mixed saliva. J. Immunol. 127:46–50.PubMedGoogle Scholar
  14. Derewenda Z. S. and Derewenda U. (1998). The structure and function of platelet-activating factor acetylhydrolases. Cell Mol. Life Sci. 54:446–455.PubMedCrossRefGoogle Scholar
  15. Farooqui A. A. and Horrocks L. A. (2004). Plasmalogens, platelet-activating factor, and other ether lipids. In: Nicolaou A. and Kokotos G. (eds.), Bioactive Lipids. Oily Press, Bridgwater, England, pp. 107–134.Google Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. Fleck M. W., Hirotsune S., Gambello M. J., Phillips-Tansey E., Suares G., Mervis R. F., Wynshaw-Boris A., and McBain C. J. (2000). Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly. J. Neurosci. 20:2439–2450.PubMedGoogle Scholar
  18. Garg A., Sridhar M. R., and Gulati S. (2007). Autosomal recessive type I lissencephaly. Indian J. Pediatr. 74:199–201.PubMedCrossRefGoogle Scholar
  19. 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.Google Scholar
  20. 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.PubMedGoogle Scholar
  21. Hattori M., Arai H., and Inoue K. (1993). Purification and characterization of bovine brain platelet-activating factor acetylhydrolase. J. Biol. Chem. 268:18748–18753.PubMedGoogle Scholar
  22. Hattori M., Adachi H., Tsujumoto M., Arai H., and Inoue K. (1994). The catalytic subunit of bovine brain platelet-activating factor acetylhydrolase is a novel type of serine esterase. J. Biol. Chem. 269:23150–23155.PubMedGoogle Scholar
  23. Hattori M., Adachi H., Aoki J., Tsujimoto M., Arai H., and Inoue K. (1995a). Cloning and expression of a cDNA encoding the beta-subunit (30-kDa subunit) of bovine brain platelet-activating factor acetylhydrolase. J Biol. Chem. 270:31345–31352.PubMedCrossRefGoogle Scholar
  24. Hattori K., Hattori M., Adachi H., Tsujimoto M., Arai H., and Inoue K. (1995b). Purification and characterization of platelet-activating factor acetylhydrolase II from bovine liver cytosol. J. Biol. Chem. 270:22308–22313.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. Hirashima Y., Ueno H., Karasawa K., Yokoyama K., Setaka M., and Takaku A. (2000). Transfection of the plasma-type platelet-activating factor acetylhydrolase gene attenuates glutamate-induced apoptosis in cultured rat cortical neurons. Brain Res. 885:128–132.PubMedCrossRefGoogle Scholar
  27. Karasawa K., Kuge O., Kawasaki K., Nishijima M., Nakano Y., Tomita M., Yokoyama K., Setaka M., ans Nojima S. (1996). Cloning, expression and characterization of plasma platelet-activating factor-acetylhydrolase from guinea pig. J. Biochem. (Tokyo). 120:838–844.Google Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. Koizumi H., Yamaguchi N., Hattori M., Ishikawa T. O., Aoki J., Taketo M. M., Inoue K., and Arai H. (2003). Targeted disruption of intracellular type I platelet activating factor-acetylhydrolase catalytic subunits cause severe impairment in spermatogenesis. J. Biol. Chem. 278:12489–12494.PubMedCrossRefGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. Lee T. C., Blank M. L., Fitzgerald V., and Snyder F. (1981). Substrate specificity in the biocleavage of the O-alkyl bond: 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid) and its metabolites. Arch. Biochem. Biophys. 208:353–357.PubMedCrossRefGoogle Scholar
  34. Lynch J. M. and Hensen P. M. (1986). The intracellular retention of newly synthesized platelet-activating factor. J. Immunol. 137:2653–2661.PubMedGoogle Scholar
  35. MacRitchie A. N., Gardner A. A., Prescott S. M., and Stafforini D. M. (2007). Molecular basis for susceptibility of plasma platelet-activating factor acetylhydrolase to oxidative inactivation. FASEB J. 21:1164–1176.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. Matsuzawa A., Hattori K., Aoki J., Arai H., and Inoue K. (1997). Protection against oxidative stress-induced cell death by intracellular platelet-activating factor-acetylhydrolase II. J Biol. Chem. 272:32315–32320.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. Miyaura S., Maki N., Byrd W., and Johnston J. M. (1991). The hormonal regulation of platelet-activating factor acetylhydrolase activity in plasma. Lipids 26:1015–1020.PubMedCrossRefGoogle Scholar
  42. Neer E. J., Schmidt C. J., Nambudripad R., and Smith T. F. (1994). The ancient regulatory-protein family of WD-repeat proteins. Nature 371:297–300.PubMedCrossRefGoogle Scholar
  43. Nishihira J. and Ishibashi T. (1986). A phospholipase C with a high specificity for platelet-activating factor in rabbit liver light mitochondria. Lipids 21:780–785.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. Quistad G. B., Fisher K. J., Owen S. C., Klintenberg R., and Casida J. E. (2005). Platelet-activating factor acetylhydrolase: Selective inhibition by potent n-alkyl methylphosphonofluoridates. Toxicol. Appl. Pharmacol. 205:149–156.PubMedCrossRefGoogle Scholar
  46. Rice S. Q. J., Southan C., Boyd H. F., Terrett J. A., Macphee C. H., Moores K., Gloger I. S., and Tew D. G. (1998). Expression, purification and characterization of a human serine-dependent phospholipase A2 with high specificity for oxidized phospholipids and platelet activating factor. Biochem. J. 330:1309–1315.PubMedGoogle Scholar
  47. Riera J., Rodriguez R., Carcedo M. T., Campa V. M., Ramos S., and Lazo P. S. (2007). Isolation and characterization of nudC from mouse macrophages, a gene implicated in the inflammatory response through the regulation of PAF-AH(I) activity. FEBS Lett. 581:3057–3062.PubMedCrossRefGoogle Scholar
  48. Sheffield R. J., McMullen T. W., Li J., Ho Y. S., Garrard S. M., Derewenda U., and Derewenda Z. S. (2001). Characterization of a platelet activating factor acetylhydrolase from rat adipocyte. Life Sci. 67:2807–2825.Google Scholar
  49. Snyder F. (1995). Platelet-activating factor: The biosynthetic and catabolic enzymes. Biochem. J. 305:689–705.PubMedGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. Soubeyrand S., Lazure C., and Manjunath P. (1998). Phospholipase A2 from bovine seminal plasma is a platelet-activating factor acetylhydrolase. Biochem. J. 29:41–47.Google Scholar
  52. Stafforini D. M., Rollins E. N., Prescott S. M., and McIntyre T. M. (1993). The platelet-activating factor acetylhydrolase from human erythrocytes. Purification and properties. J. Biol. Chem. 268:3857–3865.PubMedGoogle Scholar
  53. Stafforini D. M., Satoh K., Atkinson D. L., Tjoelker L. W., Eberhard C., Yoshida H., Imaizumi T., Takamatsu S., Zimmerman G. A., McIntyre T. M., Gray P. W., and Prescott S. M. (1996a). Platelet-activating factor acetylhydrolase deficiency A missense mutation near the active site of an anti-inflammatory phospholipase. J. Clin. Invest. 97:2784–2791.PubMedCrossRefGoogle Scholar
  54. Stafforini D. M., Prescott S. M., Zimmerman G. A., and McIntyre T. M. (1996b). Mammalian platelet-activating factor acetylhydrolases. Biochim. Biophys. Acta. 1301:161–173.PubMedGoogle Scholar
  55. Stafforini D. M., McIntyre T. M., Zimmerman G. A., and Prescott S. M. (1997). Platelet-activating factor acetylhydrolases. J. Biol. Chem. 272:17895–17898.PubMedCrossRefGoogle Scholar
  56. Stafforini D. M., Tjoelker L. W., McCormick S. P., Vaitkus D., McIntyre T. M., Gray P. M., Young S. G., and Prescott S. M. (1999). Molecular basis of the interaction between plasma platelet-activating factor acetylhydrolase and low density lipoprotein. J. Biol. Chem. 274:7018–7024.PubMedCrossRefGoogle Scholar
  57. 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. (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.PubMedCrossRefGoogle Scholar
  58. Sugimoto S., Sugimoto H., Aoyama C., Aso C., Mori M., and Izumi T. (2006). Purification and characterization of lysophospholipase D from rat brain. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 1761:1410–1418.CrossRefGoogle Scholar
  59. Tjoelker L. W., Eberhardt C., Unger J., Le Trong H., Zimmerman G. A., McIntyre T. M., Stafforini D. M., Prescott S. M., and Gray P. W. (1995). Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad. J. Biol. Chem. 270:25481–25487.PubMedCrossRefGoogle Scholar
  60. Tjoelker L. W. and Stafforini D. M. (2000). Platelet-activating factor acetylhydrolases in health and disease. Biochim. Biophys. Acta. 1488:102–123.PubMedGoogle Scholar
  61. Tokuoka S. M., Ishii S., Kawamura N., Satoh M., Shimada A., Sasaki S., Hirotsune S., Wynshaw-Boris A., and Shimizu T. (2003). Involvement of platelet-activating factor and LIS1 in neuronal migration. Eur. J. Neurosci. 18:563–570.PubMedCrossRefGoogle Scholar
  62. 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.CrossRefGoogle Scholar
  63. Tsutsumi T., Morishiqe J., Fukuzawa K., and Tokumura A. (2007). Movement of monoglyceride derived from hydrolysis of fluorescence-labeled lyso platelet-activating factor by lysophospholipase C through plasma membranes of porcine kidney epithelial cell line LLC-PK1. Prostaglandin Other Lipid Mediat. 83:33–41.CrossRefGoogle Scholar
  64. 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.PubMedCrossRefGoogle Scholar
  65. van den Bosch H., Slurk A., ten Cate J. W., and Aarsman A. J. (1991). Studies on the selectivity of enzymes involved in platelet-activating factor formation in stimulated cells. Lipids 26:967–973.PubMedCrossRefGoogle Scholar
  66. Wang D. S., Shaw R., Hattori M., Arai H., Inoue K., and Shaw G. (1995). Binding of pleckstrin homology domains to WD40/beta-transducin repeat containing segments of the protein product of the Lis-1 gene. Biochem. Biophys. Res. Commun. 209:622–629.PubMedCrossRefGoogle Scholar
  67. Wu J., Nilsson A., Jonsson B. A. G., Stenstad H., Agace W., Cheng Y. J., and Duan R. D. (2006). Intestinal alkaline sphingomyelinase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity. Biochem. J. 394:299–308.PubMedCrossRefGoogle Scholar
  68. Wykle R. L. and Schremmer J. M. (1974). A lysophospholipase D pathway in the metabolism of ether-linked lipids in brain microsomes. J. Biol. Chem. 249:1742–1746.PubMedGoogle Scholar
  69. Yoshida H., Satoh K., and Takamatsu S. (1993). Platelet-activating factor acetylhydrolase in red cell membranes. Does decreased activity impair erythrocyte deformability in ischemic stroke patients? Stroke 24:14–18.PubMedGoogle Scholar
  70. Yasuda K., Furukawa M., and Johnston J. M. (1996). Effect of estrogens on plasma platelet-activating factor acetylhydrolase and the timing of parturition in the rat. Biol. Reprod. 54:224–229.PubMedCrossRefGoogle Scholar

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