Skip to main content
SpringerLink
Log in

Role of Cytosolic Phospholipase A2 in Oxidative and Inflammatory Signaling Pathways in Different Cell Types in the Central Nervous System

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Phospholipases A2 (PLA2s) are important enzymes for the metabolism of fatty acids in membrane phospholipids. Among the three major classes of PLA2s in the mammalian system, the group IV calcium-dependent cytosolic PLA2 alpha (cPLA2α) has received the most attention because it is widely expressed in nearly all mammalian cells and its active participation in cell metabolism. Besides Ca2+ binding to its C2 domain, this enzyme can undergo a number of cell-specific post-translational modifications, including phosphorylation by protein kinases, S-nitrosylation through interaction with nitric oxide (NO), as well as interaction with other proteins and lipid molecules. Hydrolysis of phospholipids by cPLA2 yields two important lipid mediators, arachidonic acid (AA) and lysophospholipids. While AA is known to serve as a substrate for cyclooxygenases and lipoxygenases, which are enzymes for the synthesis of eicosanoids and leukotrienes, lysophospholipids are known to possess detergent-like properties capable of altering microdomains of cell membranes. An important feature of cPLA2 is its link to cell surface receptors that stimulate signaling pathways associated with activation of protein kinases and production of reactive oxygen species (ROS). In the central nervous system (CNS), cPLA2 activation has been implicated in neuronal excitation, synaptic secretion, apoptosis, cell-cell interaction, cognitive and behavioral function, oxidative-nitrosative stress, and inflammatory responses that underline the pathogenesis of a number of neurodegenerative diseases. However, the types of extracellular agonists that target intracellular signaling pathways leading to cPLA2 activation among different cell types and under different physiological and pathological conditions have not been investigated in detail. In this review, special emphasis is given to metabolic events linking cPLA2 to activation in neurons, astrocytes, microglial cells, and cerebrovascular cells. Understanding the molecular mechanism(s) for regulation of this enzyme is deemed important in the development of new therapeutic targets for the treatment and prevention of neurodegenerative diseases.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

Aβ:

Amyloid beta peptides

AA:

Arachidonic acid

AACOCF3:

Arachidonyl trifluoromethyl ketone

BEL:

Bromoenol lactone

COX:

Cyclooxygenase

CNS:

Central nervous system

CAMKII:

Calcium/calmodulin-dependent protein kinase II

cPLA2α:

Cytosolic phospholipase A2 alpha

DHA:

Docosahexaenoic acid

ERK1/2:

Extracellular signal-regulated kinases 1/2

IFN-γ:

Interferon gamma

LOX:

Lipoxygenase

LPS:

Lipopolysaccharides

MAFP:

Methyl arachidonyl fluorophosphonate

MAPK:

Mitogen-activated protein kinases

NMDA:

N-methyl-d-aspartic acid

NO:

Nitric oxide

PGE2:

Prostaglandin E2

PKC:

Protein kinase C

PMA:

Phorbol myristoyl acetate

PUFA:

Polyunsaturated fatty acids

ROS:

Reactive oxygen species

References

  1. Bazan NG Jr, Rakowski H (1970) Increased levels of brain free fatty acids after electroconvulsive shock. Life Sci 9(9):501–507

    Article  PubMed  CAS  Google Scholar 

  2. Bazan NG Jr (1970) Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218(1):1–10

    Article  PubMed  CAS  Google Scholar 

  3. Sun GY, Horrocks LA, Farooqui AA (2007) The roles of NADPH oxidase and phospholipases A2 in oxidative and inflammatory responses in neurodegenerative diseases. J Neurochem 103(1):1–16

    PubMed  CAS  Google Scholar 

  4. Sun GY et al (2010) Phospholipases A2 and inflammatory responses in the central nervous system. Neuromol Med 12(2):133–148

    Article  CAS  Google Scholar 

  5. Murakami M et al (2011) Recent progress in phospholipase A(2) research: from cells to animals to humans. Prog Lipid Res 50(2):152–192

    Article  PubMed  CAS  Google Scholar 

  6. Sun GY et al (2012) Integrating cytosolic phospholipase A(2) with oxidative/nitrosative signaling pathways in neurons: a novel therapeutic strategy for AD. Mol Neurobiol 46(1):85–95

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Rapoport SI (2013) Translational studies on regulation of brain docosahexaenoic acid (DHA) metabolism in vivo. Prostaglandins Leukot Essent Fat Acids 88(1):79–85

    Article  CAS  Google Scholar 

  8. Cheon Y et al (2012) Disturbed brain phospholipid and docosahexaenoic acid metabolism in calcium-independent phospholipase A(2)-VIA (iPLA(2)beta)-knockout mice. Biochim Biophys Acta 1821(9):1278–1286

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Calder PC (2008) The relationship between the fatty acid composition of immune cells and their function. Prostaglandins Leukot Essent Fat Acids 79(3–5):101–108

    Article  CAS  Google Scholar 

  10. Niemoller TD, Bazan NG (2010) Docosahexaenoic acid neurolipidomics. Prostaglandins Other Lipid Mediat 91(3–4):85–89

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Eady TN et al (2012) Docosahexaenoic acid signaling modulates cell survival in experimental ischemic stroke penumbra and initiates long-term repair in young and aged rats. PLoS One 7(10):e46151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Palacios-Pelaez R, Lukiw WJ, Bazan NG (2010) Omega-3 essential fatty acids modulate initiation and progression of neurodegenerative disease. Mol Neurobiol 41(2–3):367–374

    Article  PubMed  CAS  Google Scholar 

  13. Orr SK et al (2013) Unesterified docosahexaenoic acid is protective in neuroinflammation. J Neurochem 127(3):378–393

    Article  PubMed  CAS  Google Scholar 

  14. Mas E et al (2012) Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation. Clin Chem 58(10):1476–1484

    Article  PubMed  CAS  Google Scholar 

  15. Linkous A, Yazlovitskaya E (2010) Cytosolic phospholipase A2 as a mediator of disease pathogenesis. Cell Microbiol 12(10):1369–1377

    Article  PubMed  CAS  Google Scholar 

  16. Xu L et al (2008) Activation of cytosolic phospholipase A2alpha through nitric oxide-induced S-nitrosylation. Involvement of inducible nitric-oxide synthase and cyclooxygenase-2. J Biol Chem 283(6):3077–3087

    Article  PubMed  CAS  Google Scholar 

  17. Ward KE et al (2013) The molecular basis of ceramide-1-phosphate recognition by C2 domains. J Lipid Res 54(3):636–648

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Nakamura H et al (2013) Lactosylceramide interacts with and activates cytosolic phospholipase A2 alpha. J Biol Chem 288(32):23264–23272

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Kalyvas A, David S (2004) Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease. Neuron 41(3):323–335

    Article  PubMed  CAS  Google Scholar 

  20. Kalyvas A et al (2009) Differing roles for members of the phospholipase A2 superfamily in experimental autoimmune encephalomyelitis. Brain 132(Pt 5):1221–1235

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kriem B et al (2005) Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid-beta peptide. FASEB J 19(1):85–87

    PubMed  CAS  Google Scholar 

  22. Sanchez-Mejia RO, Mucke L (2010) Phospholipase A2 and arachidonic acid in Alzheimer’s disease. Biochim Biophys Acta 1801(8):784–790

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Sanchez-Mejia RO et al (2008) Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Nat Neurosci 11(11):1311–1318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Florent-Bechard S et al (2009) The essential role of lipids in Alzheimer’s disease. Biochimie 91(6):804–809

    Article  PubMed  CAS  Google Scholar 

  25. Gentile MT et al (2012) Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer’s disease pathogenesis. Mol Neurobiol 45(3):596–604

    Article  PubMed  CAS  Google Scholar 

  26. Schaeffer EL, Forlenza OV, Gattaz WF (2009) Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease. Psychopharmacology (Berl) 202(1–3):37–51

    Article  CAS  Google Scholar 

  27. Nakamura H et al (2012) Arachidonic acid metabolism via cytosolic phospholipase A2 alpha induces cytotoxicity in Niemann-Pick disease type C cells. J Cell Physiol 227(7):2847–2855

    Article  PubMed  CAS  Google Scholar 

  28. Linkous AG, Yazlovitskaya EM, Hallahan DE (2010) Cytosolic phospholipase A2 and lysophospholipids in tumor angiogenesis. J Natl Cancer Inst 102(18):1398–1412

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Saluja I et al (1999) Activation of cPLA2, PKC, and ERKs in the rat cerebral cortex during ischemia/reperfusion. Neurochem Res 24(5):669–677

    Article  PubMed  CAS  Google Scholar 

  30. Stephenson D et al (1999) Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration. Glia 27(2):110–128

    Article  PubMed  CAS  Google Scholar 

  31. Bonventre JV et al (1997) Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature 390(6660):622–625

    Article  PubMed  CAS  Google Scholar 

  32. Moon KH, et al (2014) Phospholipase A2, oxidative stress, and neurodegeneration in binge ethanol-treated organotypic slice cultures of developing rat brain. Alcohol Clin Exp Res 38(1):161–169

    Google Scholar 

  33. Tajuddin NF et al (2013) Effect of repetitive daily ethanol intoxication on adult rat brain: significant changes in phospholipase A2 enzyme levels in association with increased PARP-1 indicate neuroinflammatory pathway activation. Alcohol 47(1):39–45

    Article  PubMed  CAS  Google Scholar 

  34. Rao JS et al (2012) Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients. J Affect Disord 136(1–2):63–71

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Shelat PB et al (2008) Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J Neurochem 106(1):45–55

    Article  PubMed  CAS  Google Scholar 

  36. Brennan AM et al (2009) NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci 12(7):857–863

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Forlenza OV et al (2007) Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability. Prostaglandins Leukot Essent Fat Acids 76(1):47–55

    Article  CAS  Google Scholar 

  38. Forlenza OV, Schaeffer EL, Gattaz WF (2007) The role of phospholipase A2 in neuronal homeostasis and memory formation: implications for the pathogenesis of Alzheimer’s disease. J Neural Transm 114(2):231–238

    Article  PubMed  CAS  Google Scholar 

  39. Tsuda M, Hasegawa S, Inoue K (2007) P2X receptors-mediated cytosolic phospholipase A2 activation in primary afferent sensory neurons contributes to neuropathic pain. J Neurochem 103(4):1408–1416

    Article  PubMed  CAS  Google Scholar 

  40. Hasegawa S et al (2009) Activation of cytosolic phospholipase A2 in dorsal root ganglion neurons by Ca2+/calmodulin-dependent protein kinase II after peripheral nerve injury. Mol Pain 5:22

    Article  PubMed  PubMed Central  Google Scholar 

  41. Pavicevic Z, Leslie CC, Malik KU (2008) cPLA2 phosphorylation at serine-515 and serine-505 is required for arachidonic acid release in vascular smooth muscle cells. J Lipid Res 49(4):724–737

    Article  PubMed  CAS  Google Scholar 

  42. Fatima S et al (2003) CaM kinase IIalpha mediates norepinephrine-induced translocation of cytosolic phospholipase A2 to the nuclear envelope. J Cell Sci 116(Pt 2):353–365

    Article  PubMed  CAS  Google Scholar 

  43. Liu XB, Murray KD (2012) Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: location, location, location. Epilepsia 53(Suppl 1):45–52

    Article  PubMed  CAS  Google Scholar 

  44. Sanford SD et al (2012) Group IVA phospholipase A(2) is necessary for growth cone repulsion and collapse. J Neurochem 120(6):974–984

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Qu BX et al (2013) cPLA2alpha knockout mice exhibit abnormalities in the architecture and synapses of cortical neurons. Brain Res 1497:101–105

    Article  PubMed  CAS  Google Scholar 

  46. Antunes G, De Schutter E (2012) A stochastic signaling network mediates the probabilistic induction of cerebellar long-term depression. J Neurosci 32(27):9288–9300

    Article  PubMed  CAS  Google Scholar 

  47. He Y et al (2011) Prolonged exposure of cortical neurons to oligomeric amyloid-beta impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (−)-epigallocatechin-3-gallate. ASN Neurol 3(1):e00050

    Google Scholar 

  48. Malaplate-Armand C et al (2006) Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway. Neurobiol Dis 23(1):178–189

    Article  PubMed  CAS  Google Scholar 

  49. Sagy-Bross C, Hadad N, Levy R (2013) Cytosolic phospholipase Aalpha upregulation mediates apoptotic neuronal death induced by aggregated amyloid-beta peptide. Neurochem Int 63(6):541–550

    Article  PubMed  CAS  Google Scholar 

  50. Desbene C et al (2012) Critical role of cPLA2 in Abeta oligomer-induced neurodegeneration and memory deficit. Neurobiol Aging 33(6):1123.e17–29

    Article  CAS  Google Scholar 

  51. Chalimoniuk M et al (2009) Involvement of multiple protein kinases in cPLA2 phosphorylation, arachidonic acid release, and cell death in in vivo and in vitro models of 1-methyl-4-phenylpyridinium-induced parkinsonism—the possible key role of PKG. J Neurochem 110(1):307–317

    Article  PubMed  CAS  Google Scholar 

  52. Last V, Williams A, Werling D (2012) Inhibition of cytosolic phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with beta III tubulin. BMC Neurosci 13:106

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Sundaram JR et al (2012) Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration. J Neurosci 32(3):1020–1034

    Article  PubMed  CAS  Google Scholar 

  54. Fang XX et al (2013) Neuroprotection of interleukin-6 against NMDA-induced neurotoxicity is mediated by JAK/STAT3, MAPK/ERK, and PI3K/AKT signaling pathways. Cell Mol Neurobiol 33(2):241–251

    Article  PubMed  CAS  Google Scholar 

  55. Kishimoto K et al (2010) Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice. J Neuroinflammation 7:42

    PubMed  PubMed Central  Google Scholar 

  56. Xu J et al (2002) Role of PKC and MAPK in cytosolic PLA2 phosphorylation and arachadonic acid release in primary murine astrocytes. J Neurochem 83(2):259–270

    Article  PubMed  CAS  Google Scholar 

  57. Xu J et al (2003) Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents. Prostaglandins Leukot Essent Fat Acids 69(6):437–448

    Article  CAS  Google Scholar 

  58. Xiang Y et al (2013) Inhibition of sPLA2-IIA prevents LPS-induced neuroinflammation by suppressing ERK1/2-cPLA2alpha pathway in mice cerebral cortex. PLoS One 8(10):e77909

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Norenberg MD, Rama Rao KV, Jayakumar AR (2009) Signaling factors in the mechanism of ammonia neurotoxicity. Metab Brain Dis 24(1):103–117

    Article  PubMed  CAS  Google Scholar 

  60. Floreani NA et al (2010) Alcohol-induced interactive phosphorylation of Src and toll-like receptor regulates the secretion of inflammatory mediators by human astrocytes. J Neuroimmune Pharm 5(4):533–545

    Article  Google Scholar 

  61. Prasad VV, Nithipatikom K, Harder DR (2008) Ceramide elevates 12-hydroxyeicosatetraenoic acid levels and upregulates 12-lipoxygenase in rat primary hippocampal cell cultures containing predominantly astrocytes. Neurochem Int 53(6–8):220–229

    Article  PubMed  CAS  Google Scholar 

  62. Hsieh HL et al (2007) BK-induced COX-2 expression via PKC-delta-dependent activation of p42/p44 MAPK and NF-kappaB in astrocytes. Cell Signal 19(2):330–340

    Article  PubMed  CAS  Google Scholar 

  63. Hsieh HL et al (2006) BK-induced cytosolic phospholipase A2 expression via sequential PKC-delta, p42/p44 MAPK, and NF-kappaB activation in rat brain astrocytes. J Cell Physiol 206(1):246–254

    Article  PubMed  CAS  Google Scholar 

  64. Liao SL et al (2013) Diethylmaleate and iodoacetate in combination caused profound cell death in astrocytes. J Neurochem 127(2):271–282

    Article  PubMed  CAS  Google Scholar 

  65. Zhu D et al (2006) Phospholipases A2 mediate amyloid-beta peptide-induced mitochondrial dysfunction. J Neurosci 26(43):11111–11119

    Article  PubMed  CAS  Google Scholar 

  66. Zhu D et al (2009) NAD(P)H oxidase-mediated reactive oxygen species production alters astrocyte membrane molecular order via phospholipase A2. Biochem J 421(2):201–210

    Article  PubMed  CAS  Google Scholar 

  67. Akundi RS et al (2005) Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia 51(3):199–208

    Article  PubMed  Google Scholar 

  68. Anrather J et al (2011) Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic brain injury. PLoS One 6(10):e25916

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Suram S et al (2013) Cytosolic phospholipase A(2)alpha and eicosanoids regulate expression of genes in macrophages involved in host defense and inflammation. PLoS One 8(7):e69002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Kellom M et al (2012) Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation. BMC Neurosci 13:50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Sheng W et al (2011) Pro-inflammatory cytokines and lipopolysaccharide induce changes in cell morphology, and upregulation of ERK1/2, iNOS and sPLA(2)-IIA expression in astrocytes and microglia. J Neuroinflammation 8:121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Chuang DY et al (2013) Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells. J Neuroinflammation 10:15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Ribeiro R et al (2013) Involvement of ERK1/2, cPLA2 and NF-kappaB in microglia suppression by cannabinoid receptor agonists and antagonists. Prostaglandins Other Lipid Mediat 100–101:1–14

    Article  PubMed  Google Scholar 

  74. Vana AC et al (2011) Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter. Exp Neurol 231(1):45–55

    Article  PubMed  CAS  Google Scholar 

  75. Shibata N et al (2011) 4-Hydroxy-2-nonenal upregulates and phosphorylates cytosolic phospholipase A(2) in cultured Ra2 microglial cells via MAPK pathways. Neuropathology 31(2):122–128

    Article  PubMed  Google Scholar 

  76. Szaingurten-Solodkin I, Hadad N, Levy R (2009) Regulatory role of cytosolic phospholipase A2alpha in NADPH oxidase activity and in inducible nitric oxide synthase induction by aggregated Abeta1-42 in microglia. Glia 57(16):1727–1740

    Article  PubMed  CAS  Google Scholar 

  77. Gao J et al (1997) An interferon-gamma-activated site (GAS) is necessary for full expression of the mouse iNOS gene in response to interferon-gamma and lipopolysaccharide. J Biol Chem 272(2):1226–1230

    Article  PubMed  CAS  Google Scholar 

  78. Ji RR, Suter MR (2007) p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 3:33

    Article  PubMed  PubMed Central  Google Scholar 

  79. Matsui T et al (2010) Release of prostaglandin E(2) and nitric oxide from spinal microglia is dependent on activation of p38 mitogen-activated protein kinase. Anesth Analg 111(2):554–560

    Article  PubMed  CAS  Google Scholar 

  80. Ma L, Nagai J, Ueda H (2010) Microglial activation mediates de novo lysophosphatidic acid production in a model of neuropathic pain. J Neurochem 115(3):643–653

    Article  PubMed  CAS  Google Scholar 

  81. Ma L et al (2013) An LPA species (18:1 LPA) plays key roles in the self-amplification of spinal LPA production in the peripheral neuropathic pain model. Mol Pain 9(1):29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Alberghina M (2010) Phospholipase A(2): new lessons from endothelial cells. Microvasc Res 80(2):280–285

    Article  PubMed  CAS  Google Scholar 

  83. Askarova S et al (2011) Role of Abeta-receptor for advanced glycation endproducts interaction in oxidative stress and cytosolic phospholipase A(2) activation in astrocytes and cerebral endothelial cells. Neuroscience 199:375–385

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Zhang Q et al (2011) Activation of cytosolic phospholipase A2 downstream of the Src-phospholipase D1 (PLD1)-protein kinase C gamma (PKCgamma) signaling axis is required for hypoxia-induced pathological retinal angiogenesis. J Biol Chem 286(25):22489–22498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Anfuso CD et al (2007) Endothelial cell-pericyte cocultures induce PLA2 protein expression through activation of PKCalpha and the MAPK/ERK cascade. J Lipid Res 48(4):782–793

    Article  PubMed  CAS  Google Scholar 

  86. Salmeri M et al (2012) Involvement of PKCalpha-MAPK/ERK-phospholipase A(2) pathway in the Escherichia coli invasion of brain microvascular endothelial cells. Neurosci Lett 511(1):33–37

    Article  PubMed  CAS  Google Scholar 

  87. Maruvada R et al (2011) Host cytosolic phospholipase A(2)alpha contributes to group B Streptococcus penetration of the blood-brain barrier. Infect Immun 79(10):4088–4093

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Li Q et al (2010) PI3K-dependent host cell actin rearrangements are required for Cronobacter sakazakii invasion of human brain microvascular endothelial cells. Med Microbiol Immunol 199(4):333–340

    Article  PubMed  CAS  Google Scholar 

  89. Nito C et al (2008) Role of the p38 mitogen-activated protein kinase/cytosolic phospholipase A2 signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion. J Cereb Blood Flow Metab 28(10):1686–1696

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Zhang J et al (2012) Inhibition of cytosolic phospholipase A(2) alpha protects against focal ischemic brain damage in mice. Brain Res 1471:129–137

    Article  PubMed  CAS  Google Scholar 

  91. Spencer JP et al (2012) Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Aspects Med 33(1):83–97

    Article  PubMed  CAS  Google Scholar 

  92. Defillipo PP et al (2012) Inhibition of cPLA2 and sPLA2 activities in primary cultures of rat cortical neurons by Centella asiatica water extract. Nat Prod Commun 7(7):841–843

    PubMed  CAS  Google Scholar 

  93. Zhao Z et al (2011) Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death. J Neurochem 116(6):1057–1065

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Oh WJ et al (2013) Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling. Molecules 18(8):9195–9206

    Article  PubMed  CAS  Google Scholar 

  95. Yeh CH, et al (2013) Wogonin attenuates endotoxin-induced prostaglandin E2 and nitric oxide production via Src-ERK1/2-NFkappaB pathway in BV-2 microglial cells. Toxicol Ind Health doi:10.1177/0748233713485886

  96. Subramaniam S, Unsicker K (2010) ERK and cell death: ERK1/2 in neuronal death. FEBS J 277(1):22–29

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by NIH Grants 2P01 AG08357 from the NIA and P50AT006273 from the National Center for Complementary and Alternative Medicines (NCCAM), the Office of Dietary Supplements (ODS), and the National Cancer Institute (NCI). The help of Ms. Deborah Ratliff to proofread and edit the manuscript is much appreciated.

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Biochemistry Department, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA

    Grace Y. Sun, Jinghua Jiang & Agnes Simonyi

  2. Center for Translational Neurosciences, University of Missouri, Columbia, MO, USA

    Grace Y. Sun, Dennis Y. Chuang, Jinghua Jiang, Zezong Gu & Agnes Simonyi

  3. Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO, USA

    Grace Y. Sun, Dennis Y. Chuang, Yijia Zong, James C. M. Lee, Zezong Gu & Agnes Simonyi

  4. Bioengineering Department, University of Missouri, Columbia, MO, USA

    James C. M. Lee

  5. Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA

    Grace Y. Sun & Zezong Gu

Authors
  1. Grace Y. Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dennis Y. Chuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yijia Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinghua Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James C. M. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zezong Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Agnes Simonyi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Grace Y. Sun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, G.Y., Chuang, D.Y., Zong, Y. et al. Role of Cytosolic Phospholipase A2 in Oxidative and Inflammatory Signaling Pathways in Different Cell Types in the Central Nervous System. Mol Neurobiol 50, 6–14 (2014). https://doi.org/10.1007/s12035-014-8662-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8662-4

Keywords

Search

Navigation