Skip to main content
Log in

Modulation of phospholipase A2 activity in primary cultures of rat cortical neurons

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

In neurons, phospholipase A2 (PLA2) plays a central role in the regulation of membrane phospholipid metabolism. We have addressed the pharmacological modulation of PLA2 in primary cultures of rat cortical neurons. Inhibition curves were obtained in 4 day-in-culture neurons treated for 30 minutes with either the dual PLA2 inhibitor methyl arachidonyl fluorophosphonate (MAFP), or the iPLA2 inhibitor bromoenol lactone (BEL). Full inhibition was achieved with 100 and 250 µM of MAFP, or 10 and 20 µM of BEL. Conversely, a dose-dependent activation of PLA2 was obtained with 10–20 µg/ml of melitin. PLA2 inhibition with MAFP or BEL was not acutely toxic for cultured neurons. However, sustained inhibition of the enzyme precluded the development of neurites, and resulted in long-term loss of neuronal viability. We present a model of pharmacological challenge of PLA2 in vitro, which can be further used to address the involvement of the enzyme in neurodevelopment and neurodegeneration models.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • EJ Ackermann K Conde-Frieboes EA Dennis (1995) ArticleTitleInhibition of macrophage Ca(2+)-independent phospholipase A2 by bromoenol lactone and trifluoromethyl ketones. J Biol Chem 270 IssueID1 445–450 Occurrence Handle10.1074/jbc.270.1.445 Occurrence Handle7814408

    Article  PubMed  Google Scholar 

  • J Balsinde EA Dennis (1997) ArticleTitleFunction and inhibition of intracellular calcium-independent phospholipase A2. J Biol Chem 272 IssueID26 16069–16072 Occurrence Handle10.1074/jbc.272.26.16069 Occurrence Handle9195897

    Article  PubMed  Google Scholar 

  • J Balsinde MV Winstead EA Dennis (2002) ArticleTitlePhospholipase A2 regulation of arachidonic acid mobilization. FEBS Lett 531 IssueID1 2–6 Occurrence Handle10.1016/S0014-5793(02)03413-0 Occurrence Handle12401193

    Article  PubMed  Google Scholar 

  • JK Blusztajn M Liscovitch UI Richardson (1987) ArticleTitleSynthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. Proc Natl Acad Sci USA 84 IssueID15 5474–5477 Occurrence Handle3474663

    PubMed  Google Scholar 

  • J Chen SJ Engle JJ Seilhamer JÁ Tischfield (1994) ArticleTitleCloning and recombinant expression of a novel human low molecular weight Ca(2+)-dependent phospholipase A2. J Biol Chem 269 2365–2368 Occurrence Handle8300559

    PubMed  Google Scholar 

  • JD Clark L-L Lin RW Kriz CS Ramesha LA Sultzman AY Lin N Milona JL Knopf (1991) ArticleTitleA novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell 65 1043–1051 Occurrence Handle10.1016/0092-8674(91)90556-E Occurrence Handle1904318

    Article  PubMed  Google Scholar 

  • L Cupillard K Koumanov MG Mattei M Lazdunski G Lambeau (1997) ArticleTitleCloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2. J Biol Chem 272 15745–15752 Occurrence Handle10.1074/jbc.272.25.15745 Occurrence Handle9188469

    Article  PubMed  Google Scholar 

  • MR Emmerling CJ Moore PD Doyle RT Carroll RE Davis (1993) ArticleTitlePhospholipase A2 activation influences the processing and secretion of the amyloid precursor protein. Biochem Biophys Res Commun 197 IssueID1 292–297 Occurrence Handle10.1006/bbrc.1993.2474 Occurrence Handle8250938

    Article  PubMed  Google Scholar 

  • AA Farooqui ML Litsky T Farooqui LA Horrocks (1999) ArticleTitleInhibitors of intracellular phospholipase A2 activity: their neurochemical effects and therapeutical importance for neurological disorders. Brain Res Bull 49 IssueID3 139–153 Occurrence Handle10.1016/S0361-9230(99)00027-1 Occurrence Handle10435777

    Article  PubMed  Google Scholar 

  • I Flesch B Schmidt E Ferber (1985) ArticleTitleAcyl-chain specificity and kinetic properties of phospholipase A1 and A2 of bone E marrow-derived macrophages. Z Naturforsch [C] 40 IssueID5–6 356–363

    Google Scholar 

  • JE Fletcher L Tripolitis H Rosenberg J Beech (1993) ArticleTitleMalignant hyperthermia: halothane- and calcium-induced calcium release in skeletal muscle. Biochem Mol Biol Int 29 IssueID4 763–772 Occurrence Handle7683948

    PubMed  Google Scholar 

  • OV Forlenza EL Schaeffer WF Gattaz (2002) ArticleTitlePhospholipase A2 activity in rat embryonic brain and in primary cultures of cortical neurons. J Neural Transm 109 623–631 Occurrence Handle10.1007/s007020200051 Occurrence Handle12111454

    Article  PubMed  Google Scholar 

  • WF Gattaz M Köllisch T Thuren JA Virtanen PKJ Kinnunen (1987) ArticleTitleIncreased plasma phospholipase-A2 activity in schizophrenic patients: reduction after neuroleptic therapy. Biol Psychiatry 22 421–426 Occurrence Handle10.1016/0006-3223(87)90164-8 Occurrence Handle3567258

    Article  PubMed  Google Scholar 

  • WF Gattaz A Maras NJ Cairns R Levy H Förstl (1995a) ArticleTitleDecreased phospholipase A2 activity in Alzheimer brains. Biol Psychiatry 37 13–17 Occurrence Handle10.1016/0006-3223(94)00123-K

    Article  Google Scholar 

  • WF Gattaz A Steudle A Maras (1995b) ArticleTitleIncreased platelet phospholipase A2 in schizophrenia. Schizophr Res 16 1–6 Occurrence Handle10.1016/0920-9964(94)00060-L

    Article  Google Scholar 

  • WF Gattaz NJ Cairns R Levy H Forstl DF Braus A Maras (1996) ArticleTitleDecreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 246 IssueID3 129–131 Occurrence Handle10.1007/BF02189113 Occurrence Handle8739397

    Article  PubMed  Google Scholar 

  • WF Gattaz OV Forlenza LL Talib NR Barbosa CM Bottino (2004) ArticleTitlePlatelet phospholipase A(2) activity in Alzheimer’s disease and mild cognitive impairment. J Neural Transm 111 IssueID5 591–601 Occurrence Handle10.1007/s00702-004-0142-y Occurrence Handle15088152

    Article  PubMed  Google Scholar 

  • K Hattori H Adachi A Matsuzawa K Yamamoto M Tsujimoto J Aoki M Hattori H Arai K Inoue (1996) ArticleTitleCloning and expression of intracellular platelet-activating factor (paf) acetylhydrolase II. J Biol Chem 271 33032–33038 Occurrence Handle10.1074/jbc.271.29.17360 Occurrence Handle8955149

    Article  PubMed  Google Scholar 

  • TC Hwang SE Guggino WB Guggino (1990) ArticleTitleDirect modulation of secretory chloride channels by arachidonic and other cis unsaturated fatty acids. Proc Natl Acad Sci USA 87 IssueID15 5706–5709 Occurrence Handle1696009

    PubMed  Google Scholar 

  • A Ikemoto T Kobayashi S Watanabe H Okuyama (1997) ArticleTitleMembrane fatty acid modifications of PC12 cells by arachidonate or docosahexaenoate affect neurite outgrowth but not norepinephrine release. Neurochem Res 22 IssueID6 671–678 Occurrence Handle10.1023/A:1027393724676 Occurrence Handle9178949

    Article  PubMed  Google Scholar 

  • K Kadoyama Y Takahashi H Higashida T Tanabe T Yoshimoto (2001) ArticleTitleCyclooxygenase-2 stimulates production of amyloid beta-peptide in neuroblastoma × glioma hybrid NG108-15 cells. Biochem Biophys Res Commun 281 IssueID2 483–490 Occurrence Handle10.1006/bbrc.2001.4357 Occurrence Handle11181073

    Article  PubMed  Google Scholar 

  • D Kim DE Clapham (1989) ArticleTitlePotassium channels in cardiac cells activated by arachidonic acid and phospholipids. Science 244 IssueID4909 1174–1176 Occurrence Handle2727703

    PubMed  Google Scholar 

  • LE MacDonell FK Skinner PE Ward AI Glen AC Glen DJ Macdonald RM Boyle DF Horrobin (2000) ArticleTitleIncreased levels of cytosolic phospholipase A2 in dyslexics. Prostagland Leukot Essent Fatty Acids 63 IssueID1–2 37–39 Occurrence Handle10.1054/plef.2000.0189

    Article  Google Scholar 

  • B Miller M Sarantis SF Traynelis D Attwell (1992) ArticleTitlePotentiation of NMDA receptor currents by arachidonic acid. Nature 355 IssueID6362 722–725 Occurrence Handle1371330

    PubMed  Google Scholar 

  • T Mosmann (1983) ArticleTitleRapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65 IssueID1–2 55–63 Occurrence Handle6606682

    PubMed  Google Scholar 

  • TJ Nevalainen TJ Haapanen (1993) ArticleTitleDistribution of pancreatic (group I) and synovial-type (group II) phospholipases A2 in human tissues. Inflammation 17 IssueID4 453–464 Occurrence Handle10.1007/BF00916585 Occurrence Handle8406689

    Article  PubMed  Google Scholar 

  • M Noponen M Sanfilipo K Samanich H Ryer G Ko B Angrist A Wolkin J Rotrosen (1993) ArticleTitleElevated PLA2 activity in schizophrenics and other psychiatric patients. Biol Psychiatry 34 641–649 Occurrence Handle10.1016/0006-3223(93)90157-9 Occurrence Handle8292693

    Article  PubMed  Google Scholar 

  • BM Ross C Hudson J Erlich JJ Wars SJ Kish (1997) ArticleTitleIncreased phospholipid breakdown in schizophrenia. Arch Gen Psychiatry 54 487–494 Occurrence Handle9152103

    PubMed  Google Scholar 

  • Schaeffer EL, Gattaz WF (2004) Inhibition of Ca2+-independent phospholipase A2 in rat hippocampus impairs short- and long-term memory formation. Psychopharmacology (submitted)

  • M Simonato (1993) ArticleTitleA pathogenetic hypothesis of temporal lobe epilepsy. Pharmacol Res 27 217–225 Occurrence Handle10.1006/phrs.1993.1020 Occurrence Handle8327402

    Article  PubMed  Google Scholar 

  • WT Shier (1979) ArticleTitleActivation of high levels of endogenous phospholipase A2 in cultured cells. Proc Natl Acad Sci USA 76 195–199 Occurrence Handle106389

    PubMed  Google Scholar 

  • NR Smalheiser S Dissanayake A Kapil (1996) ArticleTitleRapid regulation of neurite outgrowth and retraction by phospholipase A2-derived arachidonic acid and its metabolites. Brain Res 721 IssueID1–2 39–48 Occurrence Handle10.1016/0006-8993(96)00134-5 Occurrence Handle8793082

    Article  PubMed  Google Scholar 

  • DT Stephenson JV Manetta DL White XG Chiou L Cox B Gitter PC May JD Sharp RM Kramer JA Clemens (1994) ArticleTitleCalcium-sensitive cytosolic phospholipase A2 (cPLA2) is expressed in human brain astrocytes. Brain Res 637 IssueID1–2 97–105 Occurrence Handle10.1016/0006-8993(94)91221-1 Occurrence Handle8180824

    Article  PubMed  Google Scholar 

  • J Tang RW Kriz N Wolfman M Shaffer J Seehra SS Jones (1997) ArticleTitleA novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs. J Biol Chem 272 8567–8575 Occurrence Handle10.1074/jbc.272.13.8567 Occurrence Handle9079687

    Article  PubMed  Google Scholar 

  • KW Underwood C Song RE Kriz XJ Chang JL Knopf LL Lin (1998) ArticleTitleA novel calcium-independent phospholipase A2, cPLA2γ, that is prenylated and contains homology to cPLA2. J Biol Chem 273 21926–21932 Occurrence Handle10.1074/jbc.273.34.21926 Occurrence Handle9705332

    Article  PubMed  Google Scholar 

  • F Visioli EB Rodriguez-de-Turco NR Kreisman NG Bazan (1994) ArticleTitleMembrane lipid degradation is related to interictal cortical activity in a series of seizures. Metab Brain Dis 9 161–170 Occurrence Handle10.1007/BF01999769 Occurrence Handle8072464

    Article  PubMed  Google Scholar 

  • EJ Williams FS Walsh P Doherty (1994) ArticleTitleThe production of arachidonic acid can account for calcium channel activation in the second messenger pathway underlying neurite outgrowth stimulated by NCAM, N-cadherin, and L1. J Neurochem 62 IssueID3 1231–1234 Occurrence Handle8113807

    PubMed  Google Scholar 

  • H Woelk K Peiler-Ichikawa (1974) ArticleTitleZur Aktivität der Phospholipase A2 gegenüber verschiedenen 1-Alk-1′-enyl-2-acyl- und 1-Alkyl-2-acyl-Verbindungen während der multiplen Sklerose. J Neurol 207 319–326 Occurrence Handle10.1007/BF00312585 Occurrence Handle4138845

    Article  PubMed  Google Scholar 

  • JK Yao S Leonard RD Reddy (2000) ArticleTitleMembrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr Res 42 IssueID1 7–17 Occurrence Handle10.1016/S0920-9964(99)00095-X Occurrence Handle10706981

    Article  PubMed  Google Scholar 

  • Y Yoshihara M Yamaji M Kawasaki Y Watanabe (1992) ArticleTitleOntogeny of cytosolic phospholipase A2 activity in rat brain. Biochem Biophys Res Commun 185 IssueID1 350–355 Occurrence Handle10.1016/S0006-291X(05)80992-1 Occurrence Handle1599471

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mendes, C., Gattaz, W., Schaeffer, E. et al. Modulation of phospholipase A2 activity in primary cultures of rat cortical neurons. J Neural Transm 112, 1297–1308 (2005). https://doi.org/10.1007/s00702-004-0271-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-004-0271-3

Navigation