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Brain Phospholipases And Their Role In Signal Transduction

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Book cover Neurobiology of Essential Fatty Acids

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 318))

Abstract

In response to stimuli, neural membranes release arachidonate which is then metabolized to biologically active eicosanoids (Chang et al., 1987). In neural membranes arachidonate is located exclusively in the sn-2position of membrane phospholipids and is released through various direct and indirect enzymic pathways. The direct pathway involves the stimulation of phospholipase A2. One indirect pathway requires the activation of phospholipase C followed by diacylglycerol and monoacylglycerol lipases. A second indirect pathway releases arachidonate by utilizing a lysophospholipase preceded by phospholipase A?. The hydrolysis of phospholipids by phospholipase D produces phosphatidic acid, which can then be hydrolyzed by a phosphatidic acid-specific phospholipase A2. The action of a phosphatase on phosphatidic acid generates diacylglycerol, which can be hydrolyzed by diacylglycerol and monoacylglycerol lipases.

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References

  • Aarsman AJ, Mynbeek G, van den Bosch H, Rothhut B, Prieur B, Comera C, Jordan L, Russo-Marie F (1987) Lipocortin inhibition of extracellular and intracellular phospholipases A2 is substrate concentration dependent. FEBS Lett 219: 176–180.

    Article  PubMed  CAS  Google Scholar 

  • Anthes JC, Eckel S, Siegel MI, Egan RW, Billah MM (1989) Phospholipase D in homogenates from HL-60 granulocytes: Implications of calcium and G protein control. Biochem Biophys Res Commun 163: 657–664.

    Article  PubMed  CAS  Google Scholar 

  • Axelrod J, Burch RM, Jelsema CL (1988) Receptor-mediated activation of phospholipase A2 via GTP-binding proteins: Arachidonic acid and its metabolites as second messengers. Trends Neurosci 11: 117–123.

    Article  PubMed  CAS  Google Scholar 

  • Ballou LR, DeWitt LM, Cheung WY (1986) Substrate-specific forms of human platelet phospholipase A2. J Biol Chem 261: 3107–3111.

    PubMed  CAS  Google Scholar 

  • Balow R-M, Tomkinson B, Ragnarsson U, Zetterqvist O (1986) Purification, substrate specificity, and classification of tripeptidyl peptidase II. J Biochem 261: 2409–2417.

    CAS  Google Scholar 

  • Billah MM and Anthes JC (1990) The regulation and cellular functions of phosphatidylcholine hydrolysis. Biochem J 269: 281–291.

    PubMed  CAS  Google Scholar 

  • Billah MM, Pai JK, Mullmann TJ, Egan RW, Siegel MI (1989) Regulation of phospholipase D in HL-60 granulocytes. Activation by phorbol esters, diglyceride, and calcium ionophore via protein kinase-independent mechanisms. J Biol Chem 264: 9069–9076.

    PubMed  CAS  Google Scholar 

  • Bocckino SB, Blackmore PF, Wilson PB, Exton JH (1987) Phosphatidate accumulation in hormone-treated hepatocytes via a phospholipase D mechanism. J Biol Chem 262: 15309–15315.

    PubMed  CAS  Google Scholar 

  • Bonventre JV (1990) Calcium in renal cells. Modulation of calcium-dependent activation of phospholipase A2. Environ Health Perspect 84: 155–162.

    PubMed  CAS  Google Scholar 

  • Burch RM, Luini A, Axelrod J (1986) Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells. Proc Natl Acad Sci USA 83: 7201–7205.

    Article  PubMed  CAS  Google Scholar 

  • Calignano A, Piomelli D, Sacktor TC, Schwartz JH (1991) A phospholipase A2-stimulating protein regulated by protein kinase C in Aplysianeurons. Mol Brain Res 9: 347–351.

    Article  PubMed  CAS  Google Scholar 

  • Carter HR, Wallace MA, Fain JN (1990) Purification and characterization of PLC-ßm, a muscarinic cholinergic regulated phospholipase C from rabbit brain membrane. Biochim Biophys Acta 1054: 119–128.

    Article  PubMed  CAS  Google Scholar 

  • Chalifa V, Mohn H, Liscovitch M (1990) A neutral phospholipase D activity from rat brain synaptic plasma membranes. J Biol Chem 265: 17512–17519.

    PubMed  CAS  Google Scholar 

  • Chalifour R and Kanfer JN (1982) Fatty acid activation and temperature perturbation of rat brain microsomal phospholipase D. J Neurochem 39: 299–305.

    Article  CAS  Google Scholar 

  • Chang J, Musser JH, McGregor H (1987) Phospholipase A2: Function and pharmacological regulation. Biochem Pharmacol 36: 2429–2436.

    Article  PubMed  CAS  Google Scholar 

  • Clark S and Dunlop M (1991) Modulation of phospholipase A2 activity by epidermal growth factor (EGF) in CHO cells transfected with human EGF receptor. Biochem J 274: 715–721.

    PubMed  CAS  Google Scholar 

  • Clark JD, Lin L-L, Kriz RW, Ramesha CS, Sultzman LA, Lin AY, Milona N, Knopf JL (1991) A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell 65: 1043–1051.

    Article  PubMed  CAS  Google Scholar 

  • Clark JD, Milona N, Knopf JL (1990) Purification of a 110-kilodalton cytosolic phospholipase A2 from the human monocytic cell line U937. Proc Natl Acad Sci USA 87: 7708–7712.

    Article  PubMed  CAS  Google Scholar 

  • Davidson FF, Dennis EA, Powell M, Glenney JR Jr (1987) Inhibition of phospholipase A2 by “lipocortins” and calpactins. J Biol Chem 262: 1698–1705.

    PubMed  CAS  Google Scholar 

  • Dennis EA, Rhee SG, Billah MM, Hannun YA (1991) Role of phospholipases in generating lipid second messengers in signal transduction. FASEB J 5: 2068–2077.

    PubMed  CAS  Google Scholar 

  • Edgar AD, Freysz L, Mandel P, Horrocks LA (1980) Phospholipid metabolism in low and high density C6 cells. Trans Am Soc Neurochem 11: 100.

    Google Scholar 

  • Fain JN (1990) Regulation of phosphoinositide-specific phospholipase C. Biochim Biophys Acta 1053: 81–88.

    Article  PubMed  CAS  Google Scholar 

  • Fain JN, Wallace MA, Wojcikiewicz RJH (1988) Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones. FASEB J 2: 2569–2574.

    PubMed  CAS  Google Scholar 

  • Farooqui AA and Horrocks LA (1991) Excitatory amino acid receptors, neural membrane phospholipid metabolism and neurological disorders. Brain Res Rev 16: 171–191.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui AA, Anderson DK, Flynn CJ, Bradel E, Means ED, Horrocks LA (1990) Stimulation of mono-and diacylglycerol lipase activities by bradykinin in neuronal-enriched cultures from mouse spinal cord. Biochem Biophys Res Commun 166: 1001–1009.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui AA, Farooqui T, Yates AJ, Horrocks LA (1988) Regulation of protein kinase C activity by various lipids. Neurochem Res 13: 499–511.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui AA, Pendley CE II, Taylor WA, Horrocks LA (1985) Studies on diacylglycerol lipases and lysophospholipases of bovine brain. In: Phospholipids in the nervous system, Vol II: Physiological role (Horrocks LA, Kanfer JN, Porcellati G, eds) pp 179–192. New York: Raven Press.

    Google Scholar 

  • Farooqui AA, Rammohan KW, Horrocks LA (1989) Isolation, characterization and regulation of diacylglycerol lipases from bovine brain. Ann NY Acad Sci 559: 25–36.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui AA, Taylor WA, Horrocks LA (1984) Separation of bovine brain mono and diacylglycerol lipases by heparin-Sepharose affinity chromatography. Biochem Biophys Res Commun 122: 1241–1246.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui AA, Taylor WA, Horrocks LA (1986a) Membrane bound diacylglycerol lipases of bovine brain. In: Phospholipid research and the nervous system. Biochemical and molecular pharmacology, Fidia Research Series (Horrocks LA, Freysz L, Toffano G, eds) pp 181–190. Italy: Liviana Press.

    Google Scholar 

  • Farooqui AA, Taylor WA, Horrocks LA (1986b) Characterization and solubilization of membrane bound diacylglycerol lipases from bovine brain. Int J Biochem 18: 991–997.

    Article  PubMed  CAS  Google Scholar 

  • Flower RJ (1988) Lipocortin and the mechanism of action of the glucocorticoids. Br J Pharmacol 94: 987–1015.

    Article  PubMed  CAS  Google Scholar 

  • Gray NCC and Strickland KP (1982a) The purification and characterization of a phospholipase A2 activity from the 106000 × g pellet (microsomal fraction) of bovine brain acting on phosphatidylinositol. Can J Biochem 60: 108–117.

    Article  PubMed  CAS  Google Scholar 

  • Gray NCC and Strickland KP (1982b) On the specificity of a phospholipase A2 from the 106000 × g pellet of bovine brain. Lipids 17: 91–96.

    Article  PubMed  CAS  Google Scholar 

  • Gronich JH, Bonventre JV, Nemenoff RA (1990) Purification of a high-molecular-mass form of phospholipase A2 from rat kidney activated at physiological calcium concentrations. Biochem J 271: 37–43.

    PubMed  CAS  Google Scholar 

  • Gustavsson L and Ailing C (1987) Formation of phosphatidylethanol in rat brain by phospholipase D. Biochem Biophys Res Commun 142: 958–963.

    Article  PubMed  CAS  Google Scholar 

  • Harafuji H and Ogawa Y (1980) Re-examination of the apparent binding constant of ethylene glycol bis(ß-aminoethyl ether)-N,N,N’,N’-tetraacetic acid with calcium around neutral pH. J Biochem (Tokyo) 87: 1305–1312

    PubMed  CAS  Google Scholar 

  • Hattori H and Kanfer JN (1985) Synaptosomal phospholipase D potential role in providing choline for acetylcholine synthesis. J Neurochem 45: 1578–1584.

    Article  PubMed  CAS  Google Scholar 

  • Hazen SL, Stuppy RJ, Gross RW (1990) Purification and characterization of canine myocardial cytosolic phospholipase A2. J Biol Chem 265: 10622–10630.

    PubMed  CAS  Google Scholar 

  • Hirashima Y, Farooqui AA, Mills JS, Horrocks LA (in press) Purification and characterization of bovine brain cytosol phospholipase A2. J Neurochem.

    Google Scholar 

  • Hirashima Y, Mills J, Farooqui AA, Horrocks LA (1990a) Purification and characai terization of bovine brain cytosol phospholipase A2. Soc Neurosci Abs 16: 538.

    Google Scholar 

  • Hirashima Y, Mills JS, Yates AJ, Horrocks LA (1990b) Phospholipase A2 activities with a plasmalogen substrate in brain and in neural tumor cells: A sensitive and specific assay using pyrenesulfonyl-labeled plasmenylethanolamine. Biochim Biophys Acta 1074: 35–40.

    Google Scholar 

  • Hirata F (1985) Receptor mediated cascade of phospholipid metabolism In: Phospholipids in the nervous system, Vol. 2 (Horrocks LA, Kanfer JN, Porcellati G, eds) pp 99–105. New York: Raven Press.

    Google Scholar 

  • Huang K-S, Li S, Fung W-JC, Hulmes JD, Reik L, Pan Y-CE, Low MG (1990) Purification and characterization of glycosyl-phosphatidylinositol-specific phospholipase D. J Biol Chem 265: 17738–17745.

    PubMed  CAS  Google Scholar 

  • Jelsema CL (1987) Light activation of phospholipase A2 in rod outer segments of bovine retina and its modulation by GTP-binding proteins. J Biol Chem 262: 163–168.

    PubMed  CAS  Google Scholar 

  • Jelsema CL and Axelrod J (1987) Stimulation of phospholipase A2 activity in bovine rod outer segments by the beta gamma subunits of transducin and its inhibition by the alpha subunit. Proc Natl Acad Sci USA 84: 3623–3627.

    Article  PubMed  CAS  Google Scholar 

  • Kanfer JN (1980) The base exchange enzymes and phospholipase D of mammalian tissues. Can J Biochem 58: 1370–1380.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy SP and Becker EL (1987) Ectophospholipase A2 activity of the rabbit peritoneal neutrophil. Int Arch Allergy Appl Immunol 83: 238–246.

    Article  PubMed  CAS  Google Scholar 

  • Khanna NC, Tokuda M, Waisman DM (1986) Phosphorylation of lipocortins in vitro by protein kinase C. Biochem Biophys Res Commun 141: 547–554.

    Article  PubMed  CAS  Google Scholar 

  • Kim DK, Suh PG, Ryu SH (1991) Purification and some properties of a phospholipase A2 from bovine platelets. Biochem Biophys Res Commun 174: 189–196.

    Article  PubMed  CAS  Google Scholar 

  • Kim U-H, Kim H-S, Rhee SG (1990) Epidermal growth factor and platelet-derived growth factor promote translocation of phospholipase C-γ from cytosol to membrane. FEBS Lett 270: 33–36.

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi M, Kanfer JN (1987) Phosphatidylethanol formation via transphosphatidylation by rat brain synaptosomal phospholipase D. J Neurochem 48: 1597–1603.

    Article  PubMed  CAS  Google Scholar 

  • Kramer RM, Jakubowski JA, Deykin D (1988) Hydrolysis of l-alkyl-2-arachidonoylsn-glycero-3-phosphocholine, a common precursor of platelet-activating factor and eicosanoids, by human platelet phospholipase A2. Biochim Biophys Acta 959: 269–279.

    Article  PubMed  CAS  Google Scholar 

  • Kramer RM, Roberts EF, Manetta J, Putnam JE (1991) The Ca2+-sensitive cytosolic phospholipase A2 is a 100-kDa protein in human monoblast U937 cells. J Biol Chem 266: 5268–5272.

    PubMed  CAS  Google Scholar 

  • Kroner EE, Peskar BA, Fischer H, Ferber E (1981) Control of arachidonic acid accumulation in bone marrow-derived macrophages by acyltransferases. J Biol Chem 256: 3690–3697.

    PubMed  CAS  Google Scholar 

  • Lavie Y and Liscovitch M (1990) Activation of phospholipase D by sphingoid bases in NG108-15 neural-derived cells. J Biol Chem 265: 3868–3872.

    PubMed  CAS  Google Scholar 

  • Liscovitch M (1989) Phosphatidylethanol biosynthesis in ethanol-exposed NG108-15 neuroblastoma X glioma hybrid cells. J Biol Chem 264: 1450–1456.

    PubMed  CAS  Google Scholar 

  • Martin TW and Michaelis K (1989) P2-Purinergic agonists stimulate phosphodiesteratic cleavage of phosphatidylcholine in endothelial cells. J Biol Chem 264: 8847–8856.

    PubMed  CAS  Google Scholar 

  • Mizuguchi M, Yamada M, Kim SU, Rhee SG (1991) Phospholipase C isozymes in neurons and glial cells in culture: An immunocytochemical and immunochemical study. Brain Res 548: 35–40.

    Article  PubMed  CAS  Google Scholar 

  • Moskowitz N, Puszkin S, Schook W (1983) Characterization of brain synaptic vesicle phospholipase A2 activity and its modulation by calmodulin, prostaglandin E2, prostaglandin F2α, cyclic AMP and ATP. J Neurochem 41: 1576–1586.

    Article  PubMed  CAS  Google Scholar 

  • Nahorski SR, Kendall DA, Batty I (1986) Receptors and phosphoinositide metabolism in the central nervous system. Biochem Pharmacol 35: 2447–2453.

    Article  PubMed  CAS  Google Scholar 

  • Nozawa Y, Nakashima S, Nagata K-I (1991) Phospholipid-mediated signaling in receptor activation of human platelets. Biochim Biophys Acta 1082: 219–238.

    Article  PubMed  CAS  Google Scholar 

  • Pepinsky RB, Tizard R, Mattaliano RJ, Sinclair LK, Miller GT, Browning JL, Chow EP, Burne C, Huang K-S, Pratt D, Wachter L, Hession C, Frey AZ, Wallner BP (1988) Five distinct calcium and phospholipid binding proteins share homology with lipocortin I. J Biol Chem 263: 10799–10811.

    PubMed  CAS  Google Scholar 

  • Qian Z and Drewes LR (1989) Muscarinic acetylcholine receptor regulates phosphatidylcholine phospholipase D in canine brain. J Biol Chem 264: 21720–21724.

    PubMed  CAS  Google Scholar 

  • Qian Z, Reddy PV, Drewes LR (1979) Guanine nucleotide-binding protein regulation of microsomal phospholipase D activity of canine cerebral cortex. J Biol Chem 254: 9761–9765.

    Google Scholar 

  • Reiser G and Hamprecht B (1985) Bradykinin causes a transient rise of intracellular Ca2+-activity in cultured neural cells. Pflugers Arch 405: 260–264.

    Article  PubMed  CAS  Google Scholar 

  • Rock CO and Jackowski S (1987) Thrombin-and nucleotide-activated phosphatidylinositol 4,5-bisphosphate phospholipase C in human platelet membranes. J Biol Chem 262: 5492–5498.

    PubMed  CAS  Google Scholar 

  • Schlaepfer DD and Haigler HT (1987) Characterization of Ca2+ dependent phospholipid binding and phosphorylation of lipocortin-I. J Biol Chem 262: 6931–6937.

    PubMed  CAS  Google Scholar 

  • Scott JA (1984) Phospholipase activity and plasma membrane homeostasis. J Theor Biol 111: 659–665.

    Article  PubMed  CAS  Google Scholar 

  • Strijbos P, Tilders F, Carey F, Forder R, Rothwell N (1990) Localization of lipocortin-1 in normal rat brain. Biochem Soc Trans 18: 1234–1235.

    PubMed  CAS  Google Scholar 

  • Sutherland CA and Amin D (1982) Relative activities of cat and dog platelet phospholipase A2 and diglyceride lipase — Selective inhibition of diglyceride lipase by RHC 80267. J Biol Chem 257: 14006–14010.

    PubMed  CAS  Google Scholar 

  • Taki T and Kanfer JN (1979) Partial purification and properties of a rat brain phospholipase D. J Biol Chem 254: 9761–9765.

    PubMed  CAS  Google Scholar 

  • Taylor SJ and Exton JH (1987) Guanine-nucleotide and hormone regulation of polyphosphoinositide phospholipase C activity of rat liver plasma membranes. Biochem J 248: 791–799.

    PubMed  CAS  Google Scholar 

  • van Kuijk FJGM, Sevanian A, Handelman GJ, Dratz EA (1987) A new role for phospholipase A2: Protection of membranes from lipid peroxidation damage. Trends Biochem Sci 12: 31–34.

    Article  Google Scholar 

  • Witter B and Kanfer JN (1985) Hydrolysis of endogenous phospholipids by rat brain microsomes. J Neurochem 44: 155–162.

    Article  PubMed  CAS  Google Scholar 

  • Wurtman RJ, Blusztajn JK, Maire JC (1985) “Autocannibalism” of choline-containing membrane phospholipids in the pathogenesis of Alzheimer’s disease —A hypothesis. Neurochem Int 7: 369–372.

    Article  PubMed  CAS  Google Scholar 

  • Yoshihara Y and Watanabe Y (1990) Translocation of phospholipase A2 from cytosol to membranes in rat brain induced by calcium ions. Biochem Biophys Res Commun 170: 484–490.

    Article  PubMed  CAS  Google Scholar 

  • Zeitler P, Wu YQ, Handwerger S (1991) Melittin stimulates phosphoinositide hydrolysis and placental lactogen release: Arachidonic acid as a link between phospholipase A2 and phospholipase C signal-transduction pathways. Life Sci 48: 2089–2095.

    Article  PubMed  CAS  Google Scholar 

  • Zian Z and Drewes LR (1991) Cross-talk between receptor-regulated phospholipase D and phospholipase D in brain. FASEB J 5: 315–319.

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biochemistry, The Ohio State University, 1645 Neil Ave., Rm 471, Columbus, OH, 43210, USA

    Akhlaq A. Farooqui, Yutaka Hirashima & Lloyd A. Horrocks

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  1. Akhlaq A. Farooqui
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  2. Yutaka Hirashima
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  3. Lloyd A. Horrocks
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Editors and Affiliations

  1. Louisiana State University Eye Center and Neuroscience Center Louisiana State University School of Medicine, New Orleans, Louisiana, USA

    Nicolas G. Bazan

  2. Dalhousie University, Nova Scotia, Canada

    Mary G. Murphy

  3. FIDIA Research Laboratories, Abano Terme, Italy

    Gino Toffano

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© 1992 Springer Science+Business Media New York

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Farooqui, A.A., Hirashima, Y., Horrocks, L.A. (1992). Brain Phospholipases And Their Role In Signal Transduction. In: Bazan, N.G., Murphy, M.G., Toffano, G. (eds) Neurobiology of Essential Fatty Acids. Advances in Experimental Medicine and Biology, vol 318. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3426-6_2

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  • DOI: https://doi.org/10.1007/978-1-4615-3426-6_2

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