Advertisement

Roles of Cytosolic and Secretory Phospholipases A2 in Oxidative and Inflammatory Signaling Pathways in the CNS

  • G. Y. Sun
  • A. Y. Sun
  • L. A. Horrocks
  • A. Simonyi
Reference work entry

Abstract:

Oxidative stress is implicated in the pathophysiology of a number of neurodegenerative diseases. There is evolving evidence for a metabolic link between reactive oxygen species (ROS) and phospholipases A2 (PLA2), enzymes that hydrolyze fatty acyl groups from the sn-2 position of membrane glycerophospholipids. Increased production of ROS and upregulation of PLA2 are important factors underlying the progression of stroke and Alzheimer’s disease. The major goal of this review is to provide recent information on the oxidative and inflammatory pathways associated with PLA2 activation in neurons and glial cells, particularly, the group IV cytosolic PLA2 and the group II secretory PLA2. Special emphasis is placed on signaling pathways and NADPH oxidase, an enzyme producing superoxide anions. Understanding the involvement of these PLA2 in the oxidative and inflammatory environment in central nervous system is an important step for developing novel therapeutic strategy for the treatment and prevention of neurodegenerative diseases.

Keywords

Cerebral Ischemia NADPH Oxidase Excessive Reactive Oxygen Species Production PLA2 Inhibitor Secretory PLA2 
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.

List of Abbreviations:

AMPA

2-amino-3-hydroxy-5-methyl-4-isoxazole propionate

CDR

clinical dementia ratings

CNS

central nervous system

DHA

docosahexaenoic acid

FFA

free fatty acids

HNE

hydroxynonenal

LTP

Long-term potentiation

M-CSF

macrophage colony stimulating factor

MDA

malondiadehyde

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PCR (qPCR)

quantitative real-time

PKC

protein kinase C

PLA2

phospholipases A2

PLC

phospholipase C

PUFA

polyunsaturated fatty acids

ROS

reactive oxygen species

SPAN

snake presynaptic PLA2 neurotoxin

TR-FIA

time-resolved fluoroimmunoassay

References

  1. Adibhatla RM, Hatcher JF. 2007. Secretory phospholipase A2 IIA is up-regulated by TNF-alpha and IL-1alpha/beta after transient focal cerebral ischemia in rat. Brain Res 1134: 199–205.PubMedGoogle Scholar
  2. Adibhatla RM, Hatcher JF, Dempsey RJ. 2003. Phospholipase A2, hydroxyl radicals, and lipid peroxidation in transient cerebral ischemia. Antioxid Redox Signal 5: 647–654.PubMedGoogle Scholar
  3. Adibhatla RM, Hatcher JF, Dempsey RJ. 2006. Lipids and lipidomics in brain injury and diseases. Aaps J 8: E314–321.PubMedGoogle Scholar
  4. Akiyama H, Barger S, Barnum S. et al. 2000. Inflammation and Alzheimer’s disease. Neurobiology of aging 21: 383–421.PubMedGoogle Scholar
  5. Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F. 2007. Neuronal damage in brain inflammation. Arch Neurol 64: 185–189.PubMedGoogle Scholar
  6. Bailey RW, Olson ED, Vu MP, Brueseke TJ, Robertson L, et al. 2007. Relationship Between Membrane Physical Properties and Secretory Phospholipase A2 Hydrolysis Kinetics in S49 Cells During Ionophore-Induced Apoptosis. Biophys J 93: 2350-2362.Google Scholar
  7. Bate C, Williams A. 2007. Squalestatin protects neurons and reduces the activation of cytoplasmic phospholipase A(2) by Abeta(1–42). Neuropharmacology.Google Scholar
  8. Bazan NG. 2003. Synaptic lipid signaling: Significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 44: 2221–2233.PubMedGoogle Scholar
  9. Bazan NG. 2005. Lipid signaling in neural plasticity, brain repair, and neuroprotection. Mol neurobiol 32: 89–103.PubMedGoogle Scholar
  10. Bazan NG. 2006. Cell survival matters: Docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends Neurosci 29: 263–271.PubMedGoogle Scholar
  11. Bazan NG. 2007. Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care 10: 136–141.PubMedGoogle Scholar
  12. Bazan NG, Aveldano de Caldironi MI, Rodriguez de Turco EB. 1981. Rapid release of free arachidonic acid in the central nervous system due to stimulation. Prog Lipid Res 20: 523–529.PubMedGoogle Scholar
  13. Bedard K, Krause KH. 2007. The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology. Physiol Rev 87: 245–313.PubMedGoogle Scholar
  14. Berridge MJ. 1987. Inositol trisphosphate and diacylglycerol: Two interacting second messengers. Annu Rev Biochem 56: 159–193.PubMedGoogle Scholar
  15. Bezzine S, Bollinger JG, Singer AG, Veatch SL, Keller SL, et al. 2002. On the binding preference of human groups IIA and X phospholipases A2 for membranes with anionic phospholipids. J Biol Chem 277: 48523–48534.PubMedGoogle Scholar
  16. Boilard E, Rouault M, Surrel F, Le Calvez C, Bezzine S, et al. 2006. Secreted phospholipase A2 inhibitors are also potent blockers of binding to the M-type receptor. Biochemistry 45: 13203–13218.PubMedGoogle Scholar
  17. Bonventre JV, Sapirstein A. 2002. Group IV cytosolic phospholipase A2 (PLA2) function: Insights from the knockout mouse. Adv Exp Med Biol 507: 25–31.PubMedGoogle Scholar
  18. Bosetti F, Weerasinghe GR. 2003. The expression of brain cyclooxygenase-2 is down-regulated in the cytosolic phospholipase A2 knockout mouse. J Neurochem 87: 1471–1477.PubMedGoogle Scholar
  19. Brady KM, Texel SJ, Kishimoto K, Koehler RC, Sapirstein A. 2006. Cytosolic phospholipase A alpha modulates NMDA neurotoxicity in mouse hippocampal cultures. Eur J Neurosci 24: 3381–3386.PubMedGoogle Scholar
  20. Butterfield DA, Yatin SM, Varadarajan S, Koppal T. 1999. Amyloid beta-peptide-associated free radical oxidative stress, neurotoxicity, and Alzheimer’s disease. Meth Enzymol 309: 746–768.PubMedGoogle Scholar
  21. Casadesus G, Smith MA, Basu S, Hua J, Capobianco DE, et al. 2007. Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease. Mol Neurodegener 2: 2.PubMedGoogle Scholar
  22. Choi SH, Langenbach R, Bosetti F. 2006. Cyclooxygenase-1 and -2 enzymes differentially regulate the brain upstream NF-kappa B pathway and downstream enzymes involved in prostaglandin biosynthesis. J Neurochem 98: 801–811.PubMedGoogle Scholar
  23. Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, et al. 2002. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 70: 462–473.PubMedGoogle Scholar
  24. Cunningham TJ, Souayah N, Jameson B, Mitchell J, Yao L. 2004. Systemic treatment of cerebral cortex lesions in rats with a new secreted phospholipase A2 inhibitor. J Neurotrauma 21: 1683–1691.PubMedGoogle Scholar
  25. Cupillard L, Mulherkar R, Gomez N, Kadam S, Valentin E, et al. 1999. Both group IB and group IIA secreted phospholipases A2 are natural ligands of the mouse 180-kDa M-type receptor. J Biol Chem 274: 7043–7051.PubMedGoogle Scholar
  26. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, et al. 2007. Abeta oligomers induce neuronal oxidative stress through an N-methyl-d-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 282: 11590–11601.PubMedGoogle Scholar
  27. DeGeorge JJ, Noronha JG, Bell J, Robinson P, Rapoport SI. 1989. Intravenous injection of [1–14C]arachidonate to examine regional brain lipid metabolism in unanesthetized rats. J Neurosci Res 24: 413–423.PubMedGoogle Scholar
  28. Dieter P, Kolada A, Kamionka S, Schadow A, Kaszkin M. 2002. Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: Regulation by Group IV cytosolic phospholipase A2, but not by Group V and Group IIA secretory phospholipase A2. Cell Signal 14: 199–204.PubMedGoogle Scholar
  29. Eerola LI, Surrel F, Nevalainen TJ, Gelb MH, Lambeau G, et al. 2006. Analysis of expression of secreted phospholipases A2 in mouse tissues at protein and mRNA levels. Biochim Biophys Acta 1761: 745–756.PubMedGoogle Scholar
  30. Evans JH, Gerber SH, Murray D, Leslie CC. 2004. The calcium binding loops of the cytosolic phospholipase A2 C2 domain specify targeting to Golgi and ER in live cells. Mol Biol Cell 15: 371–383.PubMedGoogle Scholar
  31. Farooqui AA, Horrocks LA. 2006. Phospholipase A2-generated lipid mediators in the brain:The good, the bad, and the ugly. Neuroscientist 12: 245–260.PubMedGoogle Scholar
  32. Farooqui AA, Horrocks LA, Farooqui T. 2000. Deacylation and reacylation of neural membrane glycerophospholipids. J Mol Neurosci 14: 123–135.PubMedGoogle Scholar
  33. Farooqui AA, Horrocks LA, Farooqui T. 2007. Modulation of inflammation in brain: A matter of fat. J Neurochem 101(3): 577–579.PubMedGoogle Scholar
  34. Farooqui AA, Ong WY, Horrocks LA. 2006. Inhibitors of brain phospholipase A2 activity: Their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 58: 591–620.PubMedGoogle Scholar
  35. Fatima S, Yaghini FA, Pavicevic Z, Kalyankrishna S, Jafari N, et al. 2005. Intact actin filaments are required for cytosolic phospholipase A2 translocation but not for its activation by norepinephrine in vascular smooth muscle cells. J Pharmacol Exp Ther 313: 1017–1026.PubMedGoogle Scholar
  36. Ferroni S, Valente P, Caprini M, Nobile M, Schubert P, et al. 2003. Arachidonic acid activates an open rectifier potassium channel in cultured rat cortical astrocytes. J Neurosci Res 72: 363–372.PubMedGoogle Scholar
  37. Forlenza OV, Mendes CT, Marie SK, Gattaz WF. 2007a. Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability. Prostaglandins, leukotrienes, and essential fatty acids 76: 47–55.PubMedGoogle Scholar
  38. Forlenza OV, Schaeffer EL, Gattaz WF. 2007b. The role of phospholipase A2 in neuronal homeostasis and memory formation: Implications for the pathogenesis of Alzheimer’s disease. J Neural Transm 114: 231–238.PubMedGoogle Scholar
  39. Fourcade O, Le Balle F, Fauvel J, Simon MF, Chap H. 1998. Regulation of secretory type-II phospholipase A2 and of lysophosphatidic acid synthesis. Adv Enzyme Regul 38: 99–107.PubMedGoogle Scholar
  40. Gaudreault SB, Chabot C, Gratton JP, Poirier J. 2004. The caveolin scaffolding domain modifies 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor binding properties by inhibiting phospholipase A2 activity. J Biol Chem 279: 356–362.PubMedGoogle Scholar
  41. Ghesquiere SA, Gijbels MJ, Anthonsen M, Gorp van PJ, Made van der I, et al. 2005. Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition. J Lipid Res 46: 201–210.PubMedGoogle Scholar
  42. Ghomashchi F, Stewart A, Hefner Y, Ramanadham S, Turk J, et al. 2001. A pyrrolidine-based specific inhibitor of cytosolic phospholipase A(2)alpha blocks arachidonic acid release in a variety of mammalian cells. Biochim Biophys Acta 1513: 160–166.PubMedGoogle Scholar
  43. Ghosh M, Loper R, Gelb MH, Leslie CC. 2006. Identification of the expressed form of human cytosolic phospholipase A2beta (cPLA2beta): cPLA2beta3 is a novel variant localized to mitochondria and early endosomes. J Biol Chem 281: 16615–16624.PubMedGoogle Scholar
  44. Ghosh M, Loper R, Ghomashchi F, Tucker DE, Bonventre JV, et al. 2007. Function, activity and membrane targeting of cytosolic phospholipase A2zeta in mouse lung fibroblasts. J Biol Chem 282: 11676-11686.PubMedGoogle Scholar
  45. Graziani A, Bricko V, Carmignani M, Graier WF, Groschner K. 2004. Cholesterol- and caveolin-rich membrane domains are essential for phospholipase A2-dependent EDHF formation. Cardiovasc Res 64: 234–242.PubMedGoogle Scholar
  46. Greco A, Minghetti L. 2004. Isoprostanes as biomarkers and mediators of oxidative injury in infant and adult central nervous system diseases. Curr Neurovasc Res 1: 341–354.PubMedGoogle Scholar
  47. Grewal S, Herbert SP, Ponnambalam S, Walker JH. 2005. Cytosolic phospholipase A2-alpha and cyclooxygenase-2 localize to intracellular membranes of EA.hy.926 endothelial cells that are distinct from the endoplasmic reticulum and the Golgi apparatus. FEBS J 272: 1278–1290.PubMedGoogle Scholar
  48. Han X. 2007. Neurolipidomics: Challenges and developments. Front Biosci 12: 2601–2615.PubMedGoogle Scholar
  49. Han X, Holtzman DM, McKeel DW, Jr. 2001. Plasmalogen deficiency in early Alzheimer’s disease subjects and in animal models: Molecular characterization using electrospray ionization mass spectrometry. J Neurochem 77: 1168–1180.PubMedGoogle Scholar
  50. Han WK, Sapirstein A, Hung CC, Alessandrini A, Bonventre JV. 2003. Cross-talk between cytosolic phospholipase A2 alpha (cPLA2 alpha) and secretory phospholipase A2 (sPLA2) in hydrogen peroxide-induced arachidonic acid release in murine mesangial cells: sPLA2 regulates cPLA2 alpha activity that is responsible for arachidonic acid release. J Biol Chem 278: 24153–24163.PubMedGoogle Scholar
  51. Hazan-Halevy I, Levy T, Wolak T, Lubarsky I, Levy R, et al. 2005. Stimulation of NADPH oxidase by angiotensin II in human neutrophils is mediated by ERK, p38 MAP-kinase and cytosolic phospholipase A2. J Hypertens 23: 1183–1190.PubMedGoogle Scholar
  52. Hirabayashi T, Murayama T, Shimizu T. 2004. Regulatory mechanism and physiological role of cytosolic phospholipase A2. Biol Pharm Bull 27: 1168–1173.PubMedGoogle Scholar
  53. Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, et al. 2003. Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer’s disease. J Neurol, Neurosurg Psychiatr 74: 788–789.Google Scholar
  54. Hurt-Camejo E, Camejo G, Peilot H, Oorni K, Kovanen P. 2001. Phospholipase A(2) in vascular disease. Circ Res 89: 298–304.PubMedGoogle Scholar
  55. Huwiler A, Staudt G, Kramer RM, Pfeilschifter J. 1997. Cross-talk between secretory phospholipase A2 and cytosolic phospholipase A2 in rat renal mesangial cells. Biochim Biophys Acta 1348: 257–272.PubMedGoogle Scholar
  56. Ikeno Y, Konno N, Cheon SH, Bolchi A, Ottonello S, et al. 2005. Secretory phospholipases A2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor. J Biol Chem 280: 28044–28052.PubMedGoogle Scholar
  57. Infanger DW, Sharma RV, Davisson RL. 2006. NADPH oxidases of the brain: Distribution, regulation, and function. Antioxid Redox Signal 8: 1583–1596.PubMedGoogle Scholar
  58. Kim HY. 2007. Novel metabolism of docosahexaenoic acid in neural cells. J Biol Chem 282: 18661-18665.PubMedGoogle Scholar
  59. Kishida KT, Pao M, Holland SM, Klann E. 2005. NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. J Neurochem 94: 299–306.PubMedGoogle Scholar
  60. Kolko M, de Turco EB, Diemer NH, Bazan NG. 2002. Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors. Neuroreport 13: 1963–1966.PubMedGoogle Scholar
  61. Kriem B, Sponne I, Fifre A, et al. 2005. Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid-beta peptide. FASEB J 19: 85–87.PubMedGoogle Scholar
  62. Kuwata H, Fujimoto C, Yoda E, Shimbara S, Nakatani Y, et al. 2007. A Novel Role of Group VIB Calcium-independent Phospholipase A2 (iPLA2{gamma}) in the Inducible Expression of Group IIA Secretory PLA2 in Rat Fibroblastic Cells. J Biol Chem 282: 20124–20132.PubMedGoogle Scholar
  63. Kuwata H, Nakatani Y, Murakami M, Kudo I. 1998. Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts. J Biol Chem 273: 1733–1740.PubMedGoogle Scholar
  64. Lambeth JD. 2007. Nox enzymes, ROS, and chronic disease: An example of antagonistic pleiotropy. Free Radic Biol Med 43: 332–347.PubMedGoogle Scholar
  65. Lee C, Park DW, Lee J, Lee TI, Kim YJ, et al. 2006. Secretory phospholipase A2 induces apoptosis through TNF-alpha and cytochrome c-mediated caspase cascade in murine macrophage RAW 264.7 cells. Eur J Pharmacol 536: 47–53.PubMedGoogle Scholar
  66. Leslie CC. 1997. Properties and regulation of cytosolic phospholipase A2. J Biol Chem 272: 16709–16712.PubMedGoogle Scholar
  67. Levy R. 2006. The role of cytosolic phospholipase A2-alfa in regulation of phagocytic functions. Biochim Biophys Acta 1761: 1323–1334.PubMedGoogle Scholar
  68. Li W, Xia J, Sun GY. 1999. Cytokine induction of iNOS and sPLA2 in immortalized astrocytes (DITNC): Response to genistein and pyrrolidine dithiocarbamate. J Interferon Cytokine Res 19: 121–127.PubMedGoogle Scholar
  69. Lin TN, Wang Q, Simonyi A, et al. 2004. Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain. J Neurochem 90: 637–645.PubMedGoogle Scholar
  70. Lue LF, Rydel R, Brigham EF, et al. 2001a. Inflammatory repertoire of Alzheimer’s disease and nondemented elderly microglia in vitro. Glia 35: 72–79.PubMedGoogle Scholar
  71. Lue LF, Walker DG, Rogers J. 2001b. Modeling microglial activation in Alzheimer’s disease with human postmortem microglial cultures. Neurobiol Aging 22: 945–956.PubMedGoogle Scholar
  72. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, et al. 2005. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 115: 2774–2783.PubMedGoogle Scholar
  73. Macchioni L, Corazzi L, Nardicchi V, Mannucci R, Arcuri C, et al. 2004. Rat brain cortex mitochondria release group II secretory phospholipase A(2) under reduced membrane potential. J Biol Chem 279: 37860–37869.PubMedGoogle Scholar
  74. Mathisen GH, Thorkildsen IH, Paulsen RE. 2007. Secretory PLA(2)-IIA and ROS generation in peripheral mitochondria are critical for neuronal death. Brain Res 1153: 43–51.PubMedGoogle Scholar
  75. Mattson MP. 2007. Calcium and neurodegeneration. Aging cell 6: 337–350.PubMedGoogle Scholar
  76. Megighian A, Rigoni M, Caccin P, Zordan MA, Montecucco C. 2007. A lysolecithin/fatty acid mixture promotes and then blocks neurotransmitter release at the Drosophila melanogaster larval neuromuscular junction. Neurosci Lett 416: 6–11.PubMedGoogle Scholar
  77. Milne GL, Sanchez SC, Musiek ES, Morrow JD. 2007. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nat Protoc 2: 221–226.PubMedGoogle Scholar
  78. Montine KS, Quinn JF, Zhang J, Fessel JP, Roberts LJ, et al. 2004. Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem Phys Lipids 128: 117–124.PubMedGoogle Scholar
  79. Montine TJ, Montine KS, McMahan W, Markesbery WR, Quinn JF, et al. 2005. F2-isoprostanes in Alzheimer and other neurodegenerative diseases. Antioxid Redox Signal 7: 269–275.PubMedGoogle Scholar
  80. Moses GS, Jensen MD, Lue LF, Walker DG, Sun AY, et al. 2006. Secretory PLA2-IIA: A new inflammatory factor for Alzheimer’s disease. J Neuroinflammation 3: 28.PubMedGoogle Scholar
  81. Mosior M, Six DA, Dennis EA. 1998. Group IV cytosolic phospholipase A2 binds with high affinity and specificity to phosphatidylinositol 4,5-bisphosphate resulting in dramatic increases in activity. J Biol Chem 273: 2184–2191.PubMedGoogle Scholar
  82. Mrak RE, Griffin WS. 2005. Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 26: 349–354.PubMedGoogle Scholar
  83. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. 2004. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA 101: 8491–8496.PubMedGoogle Scholar
  84. Murakami M, Koduri RS, Enomoto A, et al. 2001. Distinct arachidonate-releasing functions of mammalian secreted phospholipase A2s in human embryonic kidney 293 and rat mastocytoma RBL-2H3 cells through heparan sulfate shuttling and external plasma membrane mechanisms. J Biol Chem 276: 10083–10096.PubMedGoogle Scholar
  85. Murakami M, Kudo I. 2001. Diversity and regulatory functions of mammalian secretory phospholipase A2s. Adv Immunol 77: 163–194.PubMedGoogle Scholar
  86. Murakami M, Kudo I. 2002. Phospholipase A2. J Biochem 131: 285–292.PubMedGoogle Scholar
  87. Murakami M, Nakatani Y, Atsumi G, Inoue K, Kudo I. 1997. Regulatory functions of phospholipase A2. Crit Rev Immunol 17: 225–283.PubMedGoogle Scholar
  88. Murakami M, Yoshihara K, Shimbara S, et al. 2002. Cellular arachidonate-releasing function and inflammation-associated expression of group IIF secretory phospholipase A2. J Biol Chem 277: 19145–19155.PubMedGoogle Scholar
  89. Nakatani Y, Tanioka T, Sunaga S, Murakami M, Kudo I. 2000. Identification of a cellular protein that functionally interacts with the C2 domain of cytosolic phospholipase A(2)alpha. J Biol Chem 275: 1161–1168.PubMedGoogle Scholar
  90. Nanda BL, Nataraju A, Rajesh R, Rangappa KS, Shekar MA, et al. 2007. PLA2 mediated arachidonate free radicals: PLA2 inhibition and neutralization of free radicals by anti-oxidants new role as anti-inflammatory molecule. Curr Top Med Chem 7: 765–777.PubMedGoogle Scholar
  91. Narendra Sharath Chandra JN, Ponnappa KC, Sadashiva CT, Priya BS, Nanda BL, et al. 2007. Chemistry and structural evaluation of different phospholipase A2 inhibitors in arachidonic acid pathway mediated inflammation and snake venom toxicity. Curr Top Med Chem 7: 787–800.PubMedGoogle Scholar
  92. Nevalainen TJ, Eerola LI, Rintala E, Laine VJ, Lambeau G, et al. 2005. Time-resolved fluoroimmunoassays of the complete set of secreted phospholipases A2 in human serum. Biochim Biophys Acta 1733: 210–223.PubMedGoogle Scholar
  93. Ni Z, Okeley NM, Smart BP, Gelb MH. 2006. Intracellular actions of group IIA secreted phospholipase A2 and group IVA cytosolic phospholipase A2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells. J Biol Chem 281: 16245–16255.PubMedGoogle Scholar
  94. Nishizaki T, Nomura T, Matsuoka T, Enikolopov G, Sumikawa K. 1999. Arachidonic acid induces a long-lasting facilitation of hippocampal synaptic transmission by modulating PKC activity and nicotinic ACh receptors. Brain Res Mol Brain Res 69: 263–272.PubMedGoogle Scholar
  95. Paris D, Town T, Parker T, Humphrey J, Mullan M. 2000. beta-Amyloid vasoactivity and proinflammation in microglia can be blocked by cGMP-elevating agents. Ann N Y Acad Sci 903: 446–450.PubMedGoogle Scholar
  96. Petan T, Krizaj I, Gelb MH, Pungercar J. 2005. Ammodytoxins, potent presynaptic neurotoxins, are also highly efficient phospholipase A2 enzymes. Biochemistry 44: 12535–12545.PubMedGoogle Scholar
  97. Pettus BJ, Bielawska A, Subramanian P, et al. 2004. Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2. J Biol Chem 279: 11320–11326.PubMedGoogle Scholar
  98. Phillis JW, Horrocks LA, Farooqui AA. 2006. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: Their role and involvement in neurological disorders. Brain Res Rev 52: 201–243.PubMedGoogle Scholar
  99. Pinto F, Brenner T, Dan P, Krimsky M, Yedgar S. 2003. Extracellular phospholipase A2 inhibitors suppress central nervous system inflammation. Glia 44: 275–282.PubMedGoogle Scholar
  100. Quadros A, Patel N, Crescentini R, Crawford F, Paris D, et al. 2003. Increased TNFalpha production and Cox-2 activity in organotypic brain slice cultures from APPsw transgenic mice. Neurosci Lett 353: 66–68.PubMedGoogle Scholar
  101. Quinn MT, Ammons MC, Deleo FR. 2006. The expanding role of NADPH oxidases in health and disease: No longer just agents of death and destruction. Clin Sci (Lond) 111: 1–20.Google Scholar
  102. Rao JS, Ertley RN, Lee HJ, Rapoport SI, Bazinet RP. 2006. Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic phospholipase A2 in rat frontal cortex. Pharmacogenomics J 6: 413–420.PubMedGoogle Scholar
  103. Rao JS, Ertley RN, Rapoport SI, Bazinet RP, Lee HJ. 2007. Chronic NMDA administration to rats up-regulates frontal cortex cytosolic phospholipase A(2) and its transcription factor, activator protein-2. J Neurochem 102: 1918-1927.PubMedGoogle Scholar
  104. Rapoport SI. 2001. In vivo fatty acid incorporation into brain phosholipids in relation to plasma availability, signal transduction and membrane remodeling. J Mol Neurosci 16: 243–261; discussion 279-284.PubMedGoogle Scholar
  105. Rapoport SI. 2005. In vivo approaches and rationale for quantifying kinetics and imaging brain lipid metabolic pathways. Prostaglandins Other Lipid Mediat 77: 185–196.PubMedGoogle Scholar
  106. Rapoport SI, Chang MC, Spector AA. 2001. Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J Lipid Res 42: 678–685.PubMedGoogle Scholar
  107. Reid RC. 2005. Inhibitors of secretory phospholipase A2 group IIA. Curr Med Chem 12: 3011–3026.PubMedGoogle Scholar
  108. Rigoni M, Pizzo P, Schiavo G, Weston AE, Zatti G, et al. 2007. Calcium influx and mitochondrial alterations at synapses exposed to snake neurotoxins or their phospholipid hydrolysis products. J Biol Chem 282: 11238–11245.PubMedGoogle Scholar
  109. Rigoni M, Schiavo G, Weston AE, Caccin P, Allegrini F, et al. 2004. Snake presynaptic neurotoxins with phospholipase A2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles. J Cell Sci 117: 3561–3570.PubMedGoogle Scholar
  110. Rizzo MT, Nguyen E, Aldo-Benson M, Lambeau G. 2000. Secreted phospholipase A(2) induces vascular endothelial cell migration. Blood 96: 3809–3815.PubMedGoogle Scholar
  111. Rodriguez De Turco EB, Jackson FR, DeCoster MA, Kolko M, Bazan NG. 2002. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes. J Neurosci Res 68: 558–567.PubMedGoogle Scholar
  112. Rogers J, Webster S, Lue LF, Brachova L, Civin WH, et al. 1996. Inflammation and Alzheimer’s disease pathogenesis. Neurobiol Aging 17: 681–686.PubMedGoogle Scholar
  113. Rosenberger TA, Oki J, Purdon AD, Rapoport SI, Murphy EJ. 2002. Rapid synthesis and turnover of brain microsomal ether phospholipids in the adult rat. J Lipid Res 43: 59–68.PubMedGoogle Scholar
  114. Rosenberger TA, Villacreses NE, Hovda JT, Bosetti F, Weerasinghe G, et al. 2004. Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide. J Neurochem 88: 1168–1178.PubMedGoogle Scholar
  115. Rouault M, Le Calvez C, Boilard E, et al. 2007. Recombinant production and properties of binding of the full set of mouse secreted phospholipases A2 to the mouse M-type receptor. Biochemistry 46: 1647–1662.PubMedGoogle Scholar
  116. Samuelsson M, Fisher L, Iverfeldt K. 2005. beta-Amyloid and interleukin-1beta induce persistent NF-kappaB activation in rat primary glial cells. Int J Mol Med 16: 449–453.PubMedGoogle Scholar
  117. Sang N, Chen C. 2006. Lipid signaling and synaptic plasticity. Neuroscientist 12: 425–434.PubMedGoogle Scholar
  118. Sapirstein A, Bonventre JV. 2000. Phospholipases A2 in ischemic and toxic brain injury. Neurochem Res 25: 745–753.PubMedGoogle Scholar
  119. Schwemmer M, Aho H, Michel JB. 2001. Interleukin-1beta-induced type IIA secreted phospholipase A2 gene expression and extracellular activity in rat vascular endothelial cells. Tissue Cell 33: 233–240.PubMedGoogle Scholar
  120. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, et al. 2007. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 27: 2866–2875.PubMedGoogle Scholar
  121. Shen Y, Kishimoto K, Linden DJ, Sapirstein A. 2007. Cytosolic phospholipase A(2) alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment. Proc Natl Acad Sci USA 104: 6078–6083.PubMedGoogle Scholar
  122. Stahelin RV, Subramanian P, Vora M, Cho W, Chalfant CE. 2007. Ceramide-1-phosphate Binds Group IVA Cytosolic Phospholipase a2 via a Novel Site in the C2 Domain. J Biol Chem 282: 20467–20474.PubMedGoogle Scholar
  123. Strokin M, Sergeeva M, Reiser G. 2003. Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+. Br J Pharmacol 139: 1014–1022.PubMedGoogle Scholar
  124. Subramanian P, Stahelin RV, Szulc Z, Bielawska A, Cho W, et al. 2005. Ceramide 1-phosphate acts as a positive allosteric activator of group IVA cytosolic phospholipase A2 alpha and enhances the interaction of the enzyme with phosphatidylcholine. J Biol Chem 280: 17601–17607.PubMedGoogle Scholar
  125. Sun GY, Horrocks LA, Farooqui AA. 2007. The roles of NADPH oxidase and phospholipases A(2) in oxidative and inflammatory responses in neurodegenerative diseases. J Neurochem 103: 1-16.PubMedGoogle Scholar
  126. Sun GY, MacQuarrie RA. 1989. Deacylation-reacylation of arachidonoyl groups in cerebral phospholipids. Ann N Y Acad Sci 559: 37–55.PubMedGoogle Scholar
  127. Sun GY, Xu J, Jensen MD, Simonyi A. 2004. Phospholipase A2 in the central nervous system: Implications for neurodegenerative diseases. J Lipid Res 45: 205–213.PubMedGoogle Scholar
  128. Tabuchi S, Uozumi N, Ishii S, Shimizu Y, Watanabe T, Shimizu T. 2003. Mice deficient in cytosolic phospholipase A2 are less susceptible to cerebral ischemia/reperfusion injury. Acta Neurochir 86: 169–172.Google Scholar
  129. Taketo MM, Sonoshita M. 2002. Phospolipase A2 and apoptosis. Biochim Biophys Acta 1585: 72–76.PubMedGoogle Scholar
  130. Tanaka K, Arita H. 1995. Secretory phospholipase A2 inhibitors. Possible new anti-inflammatory agents. Agents Actions 46: 51–64.Google Scholar
  131. Tietge UJ, Pratico D, Ding T, Funk CD, Hildebrand RB, et al. 2005. Macrophage-specific expression of group IIA sPLA2 results in accelerated atherogenesis by increasing oxidative stress. J Lipid Res 46: 1604–1614.PubMedGoogle Scholar
  132. Toscano CD, Prabhu VV, Langenbach R, Becker KG, Bosetti F. 2007. Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain. Genome Biol 8: R14.PubMedGoogle Scholar
  133. Triggiani M, Granata F, Frattini A, Marone G. 2006. Activation of human inflammatory cells by secreted phospholipases A2. Biochim Biophys Acta 1761: 1289–1300.PubMedGoogle Scholar
  134. Tucker DE, Stewart A, Nallan L, Bendale P, Ghomashchi F, et al. 2005. Group IVC cytosolic phospholipase A2gamma is farnesylated and palmitoylated in mammalian cells. J Lipid Res 46: 2122–2133.PubMedGoogle Scholar
  135. Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K. 1997. Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: A possible involvement of free radicals. J Neurochem 68: 265–271.PubMedGoogle Scholar
  136. Varadarajan S, Yatin S, Aksenova M, Butterfield DA. 2000. Review: Alzheimer’s amyloid beta-peptide-associated free radical oxidative stress and neurotoxicity. J Struct Biol 130: 184–208.PubMedGoogle Scholar
  137. Wang Q, Sun AY, Simonyi A, et al. 2005. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res 82: 138–148.PubMedGoogle Scholar
  138. Wang Q, Tompkins KD, Simonyi A, Korthuis RJ, Sun AY, et al. 2006. Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus. Brain Res 1090: 182–189.PubMedGoogle Scholar
  139. Wang Q, Xu J, Rottinghaus GE, Simonyi A, Lubahn D, et al. 2002. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res 958: 439–447.PubMedGoogle Scholar
  140. Williams JH, Errington ML, Lynch MA, Bliss TV. 1989. Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature 341: 739–742.PubMedGoogle Scholar
  141. Wilson HA, Waldrip JB, Nielson KH, Judd AM, Han SK, et al. 1999. Mechanisms by which elevated intracellular calcium induces S49 cell membranes to become susceptible to the action of secretory phospholipase A2. J Biol Chem 274: 11494–11504.PubMedGoogle Scholar
  142. Xu J, Chalimoniuk M, Shu Y, Simonyi A, Sun AY, et al. 2003a. Prostaglandin E2 production in astrocytes: Regulation by cytokines, extracellular ATP, and oxidative agents. Prostaglandins, Leukot Essent Fatty Acids 69: 437–448.Google Scholar
  143. Xu J, Weng YI, Simonyi A, Krugh BW, Liao Z, et al. 2002. Role of PKC and MAPK in cytosolic PLA2 phosphorylation and arachadonic acid release in primary murine astrocytes. J Neurochem 83: 259–270.PubMedGoogle Scholar
  144. Xu J, Yu S, Sun AY, Sun, GY. 2003b. Oxidant-mediated AA release from astrocytes involves cPLA(2) and iPLA(2). Free Radic Biol Med 34: 1531–1543.PubMedGoogle Scholar
  145. Yagami T, Ueda K, Asakura K, et al. 2002. Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis. Mol Pharmacol 61: 114–126.PubMedGoogle Scholar
  146. Yagami T, Ueda K, Asakura K, et al. 2003. Human group IIA secretory phospholipase A2 potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels in cultured rat cortical neurons. J Neurochem 85: 749–758.PubMedGoogle Scholar
  147. Yagami T, Ueda K, Hata S, Kuroda T, Itoh N, et al. 2005. S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase A(2)-induced apoptosis. Neuropharmacology 49: 174–184.PubMedGoogle Scholar
  148. Yedgar S, Cohen Y, Shoseyov D. 2006. Control of phospholipase A2 activities for the treatment of inflammatory conditions. Biochim Biophys Acta 1761: 1373–1382.PubMedGoogle Scholar
  149. Zarkovic K. 2003. 4-hydroxynonenal and neurodegenerative diseases. Mol Aspects Med 24: 293–303.PubMedGoogle Scholar
  150. Zhu D, Lai Y, Shelat PB, Hu C, Sun GY, et al. 2006. Phospholipases A2 mediate amyloid-beta peptide-induced mitochondrial dysfunction. J Neurosci 26: 11111–11119.PubMedGoogle Scholar
  151. Zhu D, Tan KS, Zhang X, Sun AY, Sun GY, et al. 2005. Hydrogen peroxide alters membrane and cytoskeleton properties and increases intercellular connections in astrocytes. J Cell Sci 118: 3695–3703.PubMedGoogle Scholar
  152. Zipp F, Aktas O. 2006. The brain as a target of inflammation: Common pathways link inflammatory and neurodegenerative diseases. Trends Neurosci 29: 518–527.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • G. Y. Sun
  • A. Y. Sun
  • L. A. Horrocks
  • A. Simonyi

There are no affiliations available

Personalised recommendations