Phospholipase A2 (PLA2) generates arachidonic acid, docosahexaenoic acid, and lysophospholipids from neural membrane phospholipids. These metabolites have a variety of physiological effects by themselves and also are substrates for the synthesis of more potent lipid mediators such as eicosanoids, platelet activating factor, and 4-hydroxynonenal (4-HNE). At low concentrations, these mediators act as second messengers. They affect and modulate several cell functions, including signal transduction, gene expression, and cell proliferation, but at high concentrations, these lipid mediators cause neurotoxicity. Among the metabolites generated by PLA2, 4-HNE is the most cytotoxic metabolite and is associated with the apoptotic type of neural cell death. Levels of 4-HNE are markedly increased in neurological disorders such as Alzheimer disease, Parkinson disease, ischemia, spinal cord trauma, and head injury. The purpose of this review is to summarize and integrate the vast literature on metabolites generated by PLA2 for a wider audience. The authors hope that this discussion will jump-start more studies not only on the involvement of PLA2 in neurological disorders but also on the importance of PLA2-generated lipid mediators in physiological and pathological processes.
Akaishi T, Nakazawa K, Sato K, Ohno Y, Ito Y. 2004. 4-Hydroxynonenal modulates the long-term potentiation induced by L-type Ca2+ channel activation in the rat dentate gyrus in vitro. Neurosci Lett370:155–159.
2.
Almeida T, Cunha RA, Ribeiro JA. 1999. Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus. Brain Res826:104–111.
3.
Anliker B, Chun J. 2004. Cell surface receptors in lysophospholipid signaling. Semin Cell Dev Biol15:457–465.
4.
Barrera G, Pizzimenti S, Dianzani MU. 2004. 4-hydroxynonenal and regulation of cell cycle: effects on the pRb/E2F pathway. Free Radic Biol Med37:597–606.
5.
Bassa BV, Roh DD, Vaziri ND, Kirschenbaum MA, Kamanna VS. 1999. Lysophosphatidylcholine activates mesangial cell PKC and MAP kinase by PLCγ-1 and tyrosine kinase-Ras pathways. Am J Physiol277:F328–F337.
6.
Bernoud N, Fenart L, Molière P, Dehouck MP, Lagarde M, Cecchelli R, and others. 1999. Preferential transfer of 2-docosahexaenoyl-1-lysophosphatidylcholine through an in vitro blood-brain barrier over unesterified docosahexaenoic acid. J Neurochem72:338–345.
7.
Birgbauer E, Rao TS, Webb M. 2004. Lysolecithin induces demyelination in vitro in a cerebellar slice culture system. J Neurosci Res78:157–166.
8.
Boggs KP, Rock CO, Jackowski S. 1995. Lysophosphatidylcholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidylcholine synthesis at the CTP: phosphocholine cytidylyltransferase step. J Biol Chem270:7757–7764.
9.
Butterfield DA. 2003. Amyloid beta-peptide [1-42]-associated free radical-induced oxidative stress and neurodegeneration in Alzheimer's disease grain: Mechanisms and consequences. Curr Med Chem10:2651–2659.
10.
Calon F, Lim GP, Yang FS, Morihara T, Teter B, Ubeda O, and others. 2004. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron43:633–645.
11.
Camandola S, Poli G, Mattson MP. 2000. The lipid peroxidation product 4-hydroxy-2,3-nonenal increases AP-1-binding activity through caspase activation in neurons. J Neurochem74:159–168.
12.
Castegna A, Lauderback CM, Mohmmad-Abdul H, Butterfield DA. 2004. Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein: implications for Alzheimer's disease. Brain Res1004:193–197.
13.
Cazevieille C, Muller A, Meynier F, Dutrait N, Bonne C. 1994. Protection by prostaglandins from glutamate toxicity in cortical neurons. Neurochem Int24:395–398.
14.
Chalimoniuk M, King-Pospisil K, Pedersen WA, Malecki A, Wylegala E, Mattson MP, and others. 2004. Arachidonic acid increases choline acetyltransferase activity in spinal cord neurons through a protein kinase C-mediated mechanism. J Neurochem90:629–636.
15.
Chaudhuri P, Colles SM, Damron DS, Graham LM. 2003. Lysophosphatidylcholine inhibits endothelial cell migration by increasing intracellular calcium and activating calpain. Arterioscler Thromb Vasc Biol23:218–223.
16.
Chiarpotto E, Domenicotti C, Paola D, Vitali A, Nitti M, Pronzato MA, and others. 1999. Regulation of rat hepatocyte protein kinase C beta isoenzymes by the lipid peroxidation product 4-hydroxy-2,3-nonenal: a signaling pathway to modulate vesicular transport of glycoproteins. Hepatology29:1565–1572.
17.
Cox DA, Cohen ML. 1996. Lysophosphatidylcholine stimulates phospholipase D in human coronary endothelial cells: role of PKC. Am J Physiol Heart Circ Physiol271:H1706–H1710.
18.
Del Corso A, Dal Monte M, Vilardo PG, Cecconi I, Moschini R, Banditelli S, and others. 1998. Site-specific inactivation of aldose reductase by 4-hydroxynonenal. Arch Biochem Biophys350:245–248.
19.
Demediuk P, Saunders RD, Anderson DK, Means ED, Horrocks LA. 1985. Membrane lipid changes in laminectomized and traumatized cat spinal cord. Proc Natl Acad Sci U S A82:7071–7075.
20.
Dickinson DA, Iles KE, Watanabe N, Iwamoto T, Zhang H, Krzywanski DM, and others. 2002. 4-hydroxynonenal induces glutamate cysteine ligase through JNK in HBE1 cells. Free Radic Biol Med33:974–987.
21.
Doolan CM, Keenan AK. 1994. Inhibition by fatty acids of cyclic AMP-dependent protein kinase activity in brush border membranes isolated from human placental vesicles. Br J Pharmacol111:509–514.
22.
Doug M, Guda K, Nambiar PR, Rezaie A, Belinsky GS, Lambeau G, and others. 2003. Inverse association between phospholipase A2 and COX-2 expression during mouse colon tumorigenesis. Carcinogenesis24:307–315.
23.
Durante W, Liao L, Peyton KJ, Schafer AI. 1997. Lysophosphatidylcholine regulates cationic amino acid transport and metabolism in vascular smooth muscle cells. Role in polyamine biosynthesis. J Biol Chem272:30154–30159.
24.
Edgar AD, Strosznajder J, Horrocks LA. 1982. Activation of ethanol-amine phospholipase A2 in brain during ischemia. J Neurochem39:1111–1116.
25.
Esterbauer H, Schaur RJ, Zollner H. 1991. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med11:81–128.
26.
Fang X, Gibson S, Flowers M, Furui T, Bast RC Jr, Mills GB. 1997. Lysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal kinase activity. J Biol Chem272:13683–13689.
27.
Farooqui AA, Horrocks LA. 1994. Excitotoxicity and neurological disorders: involvement of membrane phospholipids. Int Rev Neurobiol36:267–323.
28.
Farooqui AA, Horrocks LA. 2004. Plasmalogens, platelet activating factor, and other ether lipids. In: Nicolaou A, Kokotos G, editors. Bioactive lipids. Bridgwater, UK: Oily Press. p 107–134.
29.
Farooqui AA, Horrocks LA, Farooqui T. 2000. Deacylation and reacylation of neural membrane glycerophospholipids. J Mol Neurosci14:123–135.
30.
Farooqui AA, Ong WY, Horrocks LA. 2003a. Plasmalogens, docosahexaenoic acid, and neurological disorders. In: Roels F, Baes M, de Bies S, editors. Peroxisomal disorders and regulation of genes. London: Kluwer Academic/Plenum. p 335–354.
31.
Farooqui AA, Ong WY, Horrocks LA. 2003b. Stimulation of lipases and phospholipases in Alzheimer disease. In: Szuhaj B, van Nieuwenhuyzen W, editors. Nutrition and biochemistry of phospholipids. Champaign, IL: AOCS. p 14–29.
32.
Farooqui AA, Ong WY, Horrocks LA. 2004. Biochemical aspects of neurodegeneration in human brain: involvement of neural membrane phospholipids and phospholipases A2. Neurochem Res29:1961–1977.
33.
Farooqui AA, Ong WY, Horrocks LA, Farooqui T. 2000. Brain cytosolic phospholipase A2: localization, role, and involvement in neurological diseases. Neuroscientist6:169–180.
34.
Farooqui AA, Ong WY, Lu XR, Halliwell B, Horrocks LA. 2001. Neurochemical consequences of kainate-induced toxicity in brain: involvement of arachidonic acid release and prevention of toxicity by phospholipase A2 inhibitors. Brain Res Rev38:61–78.
35.
Farooqui AA, Ong WY, Lu XR, Horrocks LA. 2002. Cytosolic phospholipase A2 inhibitors as therapeutic agents for neural cell injury. Curr Med Chem - Anti-Inflamm Anti-Allergy Agents1:193–204.
36.
Farooqui AA, Rosenberger TA, Horrocks LA. 1997. Arachidonic acid, neurotrauma, and neurodegenerative diseases. In: Yehuda S, Mostofsky DI, editors. Handbook of essential fatty acid biology. Totowa, NJ: Humana Press. p 277–295.
37.
Farooqui AA, Yang HC, Rosenberger TA, Horrocks LA. 1997. Phospholipase A2 and its role in brain tissue. J Neurochem69:889–901.
38.
Fiebich BL, Hüll M, Lieb K, Gyufko K, Berger M, Bauer J. 1997. Prostaglandin E2 induces interleukin-6 synthesis in human astrocytoma cells. J Neurochem68:704–709.
39.
Friguet B, Stadtman ER, Szweda LI. 1994. Modification of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. J Biol Chem269:21639–21643.
40.
Garrido R, Mattson MP, Hennig B, Toborek M. 2001. Nicotine protects against arachidonic-acid-induced caspase activation, cytochrome c release and apoptosis of cultured spinal cord neurons. J Neurochem76:1395–1403.
41.
Gómez-Muñoz A, O'Brien L, Hundal R, Steinbrecher UP. 1999. Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages. J Lipid Res40:988–993.
42.
Haag M, Magada ON, Claassen N, Bohmer LH, Kruger MC. 2003. Omega-3 fatty acids modulate ATPases involved in duodenal Ca absorption. Prostaglandins Leukot Essent Fatty Acids68:423–429.
43.
Hamano H, Nabekura J, Nishikawa M, Ogawa T. 1996. Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat. J Neurophysiol75:1264–1270.
44.
Hirabayashi T, Shimizu T. 2000. Localization and regulation of cytosolic phospholipase A2. Biochim Biophys Acta1488:124–138.
45.
Homayoun P, Rodriguez de Turco EB, Parkins NE, Lane DC, Soblosky J, Carey ME, and others. 1997. Delayed phospholipid degradation in rat brain after traumatic brain injury. J Neurochem69:199–205.
46.
Horrocks LA, Farooqui AA. 2004. Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fatty Acids70:361–372.
47.
Hossain MS, Hashimoto M, Gamoh S, Masumura S. 1999. Antioxidative effects of docosahexaenoic acid in the cerebrum versus cerebellum and brainstem of aged hypercholesterolemic rats. J Neurochem72:1133–1138.
48.
Ji C, Amarnath V, Pietenpol JA, Marnett LJ. 2001. 4-hydroxynonenal induces apoptosis via caspase-3 activation and cytochrome c release. Chem Res Toxicol14:1090–1096.
49.
Kadoya A, Miyake H, Ohyashiki T. 2003. Contribution of lipid dynamics on the inhibition of bovine brain synaptosomal Na+-K+-ATPase activity induced by 4-hydroxy-2-nonenal. Biol Pharm Bull26:787–793.
50.
Kanfer JN, Sorrentino G, Sitar DS. 1998. Phospholipases as mediators of amyloid -peptide neurotoxicity: an early event contributing to neurodegeneration characteristic of Alzheimer's disease. Neurosci Lett257:93–96.
51.
Katsuki H, Okuda S. 1995. Arachidonic acid as a neurotoxic and neurotrophic substance. Prog Neurobiol46:607–636.
52.
Keller JN, Mark RJ, Bruce AJ, Blanc E, Rothstein JD, Uchida K, and others. 1997. 4-hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience80:685–696.
53.
Keller JN, Mattson MP. 1998. Roles of lipid peroxidation in modulation of cellular signaling pathways, cell dysfunction, and death in the nervous system. Rev Neurosci9:105–116.
54.
Kiaei M, Kipiani K, Petri S, Choi DK, Chen JY, Calingasan NY, and others. 2005. Integrative role of cPLA2 with COX-2 and the effect of non-steroidal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem93:403–411.
55.
Kim DK, Rordorf G, Nemenoff RA, Koroshetz WJ, Bonventre JV. 1995. Glutamate stably enhances the activity of two cytosolic forms of phospholipase A2 in brain cortical cultures. Biochem J310:83–90.
56.
Kristal BS, Park BK, Yu BP. 1996. 4-hydroxyhexenal is a potent inducer of the mitochondrial permeability transition. J Biol Chem271:6033–6038.
Lauderback CM, Hackett JM, Huang FF, Keller JN, Szweda LI, Markesbery WR, and others. 2001. The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Aβ1-42. J Neurochem78:413–416.
59.
Lee JY, Je JH, Jung KJ, Yu BP, Chung HY. 2004. Induction of endothelial iNOS by 4-hydroxyhexenal through NF-κB activation. Free Radic Biol Med37:539–548.
60.
Légrádi A, Chitu V, Szukacsov V, Fajka-Boja R, Szücs KS, Monostori E. 2004. Lysophosphatidylcholine is a regulator of tyrosine kinase activity and intracellular Ca2+ level in Jurkat T cell line. Immunol Lett91:17–21.
61.
Leist M, Nicotera P. 1998. Apoptosis, excitotoxicity, and neuropathology. Exp Cell Res239:183–201.
62.
Lim GP, Calon F, Morihara T, Yang FS, Teter B, Ubeda O, and others. 2005. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci25:3032–3040.
63.
Lin TN, Wang Q, Simonyi A, Chen JJ, Cheung WM, He YY, and others. 2004. Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain. J Neurochem90:637–645.
64.
Liu DX, Li LP, Augustus L. 2001. Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death: a site of the neuroprotective action of methylprednisolone. J Neurochem77:1036–1047.
65.
Lu C, Chan SL, Haughey N, Lee WT, Mattson MP. 2001. Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on N-methyl-D-aspartate channels. J Neurochem78:577–589.
66.
Lucas KK, Svensson CI, Hua XY, Yaksh TL, Dennis EA. 2005. Spinal phospholipase A2 in inflammatory hyperalgesia: role of Group IVA cPLA2. Br J Pharmacol144:940–952.
67.
Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, and others. 2005. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest115:2274–2283.
68.
Lynch MA, Voss KL. 1990. Arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue. J Neurochem55:215–221.
69.
Macchioni L, Corazzi L, Nardicchi V, Mannucci R, Arcuri C, Porcellati S, and others. 2004. Rat brain cortex mitochondria release group II secretory phospholipase A2 under reduced membrane potential. J Biol Chem279:37860–37869.
70.
Maingret F, Patel AJ, Lesage F, Lazdunski M, Honoré E. 2000. Lysophospholipids open the two-pore domain mechano-gated K+channels TREK-1 and TRAAK. J Biol Chem275:10128–10133.
71.
Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, and others. 2003. Novel docosanoids inhibit brain ischemiareperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem278:43807–43817.
72.
Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP. 1997. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem68:255–264.
73.
Martínez-Cayuela M. 1995. Oxygen free radicals and human disease. Biochimie77:147–161.
74.
McIntosh TK, Saatman KE, Raghupathi R, Graham DI, Smith DH, Lee VM, and others. 1998. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol24:251–267.
75.
McKracken E, Graham DI, Nilsen M, Stewart J, Nicoll JA, Horsburgh K. 2001. 4-hydroxynonenal immunoreactivity is increased in human hippocampus after global ischemia. Brain Pathol11:414–421.
76.
Mertsch K, Blasig I, Grune T. 2001. 4-hydroxynonenal impairs the permeability of an in vitro rat blood-brain barrier. Neurosci Lett314:135–138.
77.
Millanvoye-Van Brussel E, Topal G, Brunet A, Do Phaw T, Deckert V, Rendu F, and others. 2004. Lysophosphatidylcholine and 7-oxocho-lesterol modulate Ca2+ signals and inhibit the phosphorylation of endothelial NO synthase and cytosolic phospholipase A2. Biochem J380:533–539.
78.
Mulder C, Wahlund LO, Teerlink T, Blomberg M, Veerhuis R, Van Kamp GJ, and others. 2003. Decreased lysophosphatidylcholine/ phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer's disease. J Neural Transm110:949–955.
79.
Murakami K, Routtenberg A. 2003. The role of fatty acids in synaptic growth and plasticity. In: Peet M, Glen L, Horrobin DF, editors. Phospholipid spectrum disorders in psychiatry and neurology. 2nd ed.Carnforth, Lancashire: Marius. p 77–92.
80.
Natarajan V, Scribner WM, Taher MM. 1993. 4-hydroxynonenal, a metabolite of lipid peroxidation, activates phospholipase D in vascular endothelial cells. Free Radical Biol Med15:365–375.
81.
Neely MD, Sidell KR, Graham DG, Montine TJ. 1999. The lipid peroxidation product 4-hydroxynonenal inhibits neurite outgrowth, disrupts neuronal microtubules, and modifies cellular tubulin. J Neurochem72:2323–2333.
82.
Okada M, Amamoto T, Tomonaga M, Kawachi A, Yazawa K, Mine K, and others. 1996. The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats. Neuroscience71:17–25.
83.
Ong WY, Hu CY, Hjelle OP, Ottersen OP, Halliwell B. 2000. Changes in glutathione in the hippocampus of rats injected with kainate: depletion in neurons and upregulation in glia. Exp Brain Res132:510–516.
84.
Page S, Fischer C, Baumgartner B, Haas M, Kreusel U, Loidl G, and others. 1999. 4-hydroxynonenal prevents NF-κB activation and tumor necrosis factor expression by inhibiting IκB phosphorylation and subsequent proteolysis. J Biol Chem274:11611–11618.
85.
Paradisi L, Panagini C, Parola M, Barrera G, Dianzani MU. 1985. Effects of 4-hydroxynonenal on adenylate cyclase and 5'-nucleotidase activities in rat liver plasma membranes. Chem Biol Interact53:209–217.
86.
Pettegrew JW, Klunk WE, Kanal E, Panchalingam K, McClure RJ. 1995. Changes in brain membrane phospholipid and highenergy phosphate metabolism precede dementia. Neurobiol Aging16:973–975.
87.
Phillis JW, O'Regan MH. 2004. A potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders. Brain Res Rev44:13–47.
88.
Picklo MJ, Amarnath V, McIntyre JO, Graham DG, Montine TJ. 1999. 4-Hydroxy-2(E)-nonenal inhibits CNS mitochondrial respiration at multiple sites. J Neurochem72:1617–1624.
89.
Picklo MJ, Olson SJ, Markesbery WR, Montine TJ. 2001. Expression and activities of aldo-keto oxidoreductases in Alzheimer disease. J Neuropathol Exp Neurol60:686–695.
90.
Prasad KN, La Rosa FG, Prasad JE. 1998. Prostaglandins act as neurotoxin for differentiated neuroblastoma cells in culture and increase levels of ubiquitin and beta-amyloid. In Vitro Cell Dev Biol Anim34:265–274.
91.
Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR. 1998. Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem Res23:81–88.
92.
Rao KV, Vaidyanathan VV, Sastry PS. 1994. Diacylglycerol kinase is stimulated by arachidonic acid in neural membranes. J Neurochem63:1454–1459.
93.
Rapoport SI. 1999. In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling. Neurochem Res24:1403–1415.
94.
Ray P, Ray R, Broomfield CA, Berman JD. 1994. Inhibition of bioenergetics alters intracellular calcium, membrane composition, and fluidity in a neuronal cell line. Neurochem Res19:57–63.
95.
Rikitake Y, Hirata K, Kawashima S, Takeuchi S, Shimokawa Y, Kojima Y, and others. 2001. Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine. Biochem Biophys Res Commun281:1291–1297.
96.
Rossi MA, Di Mauro C, Dianzani MU. 1993. Action of lipid peroxidation products on phosphoinositide specific phospholipase C. Mol Aspects Med14:273–279.
97.
Sakata A, Ida E, Tominaga M, Onoue K. 1987. Arachidonic acid acts as an intracellular activator of NADPH-oxidase inFc gamma receptor-mediated superoxide generation in macrophages. J Immunol138:4353–4359.
98.
Schapira AH. 1996. Oxidative stress and mitochondrial dysfunction in neurodegeneration. Curr Opin Neurol9:260–264.
99.
Schilling T, Lehmann F, Ruckert B, Eder C. 2004. Physiological mechanisms of lysophosphatidylcholine-induced de-ramification of murine microglia. J Physiol (Lond)557:105–120.
100.
Selley ML, Close DR, Stern SE. 2002. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging23:383–388.
101.
Serhan CN. 2005. Novel ω-3-derived local mediators in anti-inflammation and resolution. Pharmacol Ther105:7–21.
102.
Shibata N, Yamada S, Uchida K, Hirano A, Sakoda S, Fujimura H, and others. 2004. Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis. Brain Res1019:170–177.
103.
Shohami E, Shapira Y, Yadid G, Reisfeld N, Yedgar S. 1989. Brain phospholipase A2 is activated after experimental closed head injury in the rat. J Neurochem53:1541–1546.
104.
Springer JE, Azbill RD, Mark RJ, Begley JG, Wäg G, Mattson MP. 1997. 4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake. J Neurochem68:2469–2476.
105.
Stephenson D, Rash K, Smalstig B, Roberts E, Johnstone E, Sharp J, and others. 1999. Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration. Glia27:110–128.
106.
Stillwell W, Wassall SR. 2003. Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids126:1–27.
107.
Stone SJ, Cui Z, Vance JE. 1998. Cloning and expression of mouse liver phosphatidylserine synthase-1 cDNA—overexpression in rat hepatoma cells inhibits the CDP-ethanolamine pathway for phosphatidylethanolamine biosynthesis. J Biol Chem273:7293–7302.
108.
Subramaniam R, Roediger F, Jordan B, Mattson MP, Keller JN, Wäg G, and others. 1997. The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the conformation of cortical synaptosomal membrane proteins. J Neurochem69:1161–1169.
109.
Sun GY, Foudin LL. 1984. On the status of lysolecithin in rat cerebral cortex during ischemia. J Neurochem43:1081–1086.
110.
Sun GY, MacQuarrie RA. 1989. Deacylation-reacylation of arachidonoyl groups in cerebral phospholipids. Ann N Y Acad Sci559:37–55.
111.
Sun GY, Xu J, Jensen MD, Simonyi A. 2004a. Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J Lipid Res45:205–213.
112.
Sun GY, Xu JF, Jensen MD, Simonyi A. 2004b. Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J Lipid Res45:205–213.
113.
Tamagno E, Robino G, Obbili A, Bardini P, Aragno M, Parola M, and others. 2003. H2O2 and 4-hydroxynonenal mediate amyloid betainduced neuronal apoptosis by activating JNKs and p38MAPK. Exp Neurol180:144–155.
114.
Taylor WA. 1988. Effects of impact injury of rat spinal cord on activities of some enzymes of lipid hydrolysis [Dissertation]. Columbus: The Ohio State University.
115.
Toborek M, Garrido R, Malecki A, Kaiser S, Mattson MP, Hennig B, and others. 2000. Nicotine attenuates arachidonic acid-induced overexpression of nitric oxide synthase in cultured spinal cord neurons. Exp Neurol161:609–620.
116.
Toborek M, Malecki A, Garrido R, Mattson MP, Hennig B, Young B. 1999. Arachidonic acid-induced oxidative injury to cultured spinal cord neurons. J Neurochem73:684–692.
117.
Uchida K. 2003. 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res42:318–343.
118.
West JD, Ji C, Duncan ST, Amarnath V, Schneider C, Rizzo CJ, and others. 2004. Induction of apoptosis in colorectal carcinoma cells treated with 4-hydroxy-2-nonenal and structurally related aldehydic products of lipid peroxidation. Chem Res Toxicol17:453–462.
Woodruff RH, Franklin RJM. 1999. The expression of myelin protein mRNAs during remyelination of lysolecithin-induced demyelination. Neuropathol Appl Neurobiol25:226–235.
121.
Xu J, Chalimoniuk M, Shu Y, Simonyi A, Sun AY, Gonzalez FA, and others. 2003. Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents. Prostaglandins Leukot Essent Fatty Acids69:437–448.
122.
Yagami T, Ueda K, Asakura K, Hata S, Kuroda T, Sakaeda T, and others. 2002. Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis. Mol Pharmacol61:114–126.
123.
Yegin A, Akbas SH, Ozben T, Korgun DK. 2002. Secretory phospholipase A2 and phospholipids in neural membranes in an experimental epilepsy model. Acta Neurol Scand106:258–262.
124.
Yeo JF, Ong WY, Ling SF, Farooqui AA. 2004. Intracerebroventricular injection of phospholipases A2 inhibitors modulates allodynia after facial carrageenan injection in mice. Pain112:148–155.
125.
Yoshinaga N, Yasuda Y, Murayama T, Nomura Y. 2000. Possible involvement of cytosolic phospholipase A2 in cell death induced by 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in GH3 cells. Brain Res855:244–251.
126.
Yuan Y, Schoenwaelder SM, Salem HH, Jackson SP. 1996. The bioactive phospholipid, lysophosphatidylcholine, induces cellular effects via G-protein-dependent activation of adenylyl cyclase. J Biol Chem271:27090–27098.
127.
Zarkovic K. 2003. 4-hydroxynonenal and neurodegenerative diseases. Mol Aspects Med24:293–303.
128.
Zhang DQ, Dhillon HS, Mattson MP, Yurek DM, Prasad RM. 1999. Immunohistochemical detection of the lipid peroxidation product 4-hydroxynonenal after experimental brain injury in the rat. Neurosci Lett272:57–61.
129.
Zhang J, Hannun YA, Obeid LM. 1999. A novel assay for apoptotic body formation and membrane release during apoptosis. Cell Death Differ6:596–598.
130.
Zhang JP, Sun GY. 1995. Free fatty acids, neutral glycerides, and phosphoglycerides in transient focal cerebral ischemia. J Neurochem64:1688–1695.
