Skip to main content

Advertisement

Log in

Studies on Plasmalogen-Selective Phospholipase A2 in Brain

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Plasmalogen-selective phospholipase A2 (PlsEtn-PLA2) has been purified from pig brain using multiple column chromatographic procedure. The purified enzyme migrates as a single band on polyacrylamide. It is stimulated by Triton X-100 and inhibited by sodium deoxycholate. Purified PlsEtn-PLA2 is inhibited by iodoacetate, and this inhibition can be prevented by β-meracaptoethanol. Treatment of neuronal cell cultures with kainic acid stimulates PlsEtn-PLA2 activity in a dose-dependent manner, and this stimulation can be blocked by Ly294486, a selective kainic acid receptor antagonist. Activities of PlsEtn-PLA2 are markedly increased in plasma membrane and synaptosomal plasma membrane fraction prepared from nucleus basalis and hippocampal region of brains from Alzheimer disease patients compared to age-matched controls. It is proposed that accumulation of ceramide and increased expression of cytokines may be responsible for the stimulation of PlsEtn-PLA2 in Alzheimer disease.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Farooqui AA, Ong WY, Horrocks LA, Farooqui T (2000) Brain cytosolic phospholipase A2: localization, role, and involvement in neurological diseases. Neuroscientist 6:169–180

    Article  CAS  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. Phillis JW, O'Regan MH (2004) A potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders. Brain Res Brain Res Rev 44:13–47

    Article  CAS  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. Green JT, Orr SK, Bazinet RP (2008) The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids. J Lipid Res 49:939–944

    Article  CAS  PubMed  Google Scholar 

  6. Farooqui AA, Horrocks LA (2001) Plasmalogens: workhorse lipids of membranes in normal and injured neurons and glia. Neuroscientist 7:232–245

    Article  CAS  PubMed  Google Scholar 

  7. Hirashima Y, Farooqui AA, Mills JS, Horrocks LA (1992) Identification and purification of calcium-independent phospholipase A2 from bovine brain cytosol. J Neurochem 59:708–714

    Article  CAS  PubMed  Google Scholar 

  8. Yang H-C, Farooqui AA, Horrocks LA (1994) Effects of sialic acid and sialoglycoconjugates on cytosolic phospholipases A2 from bovine brain. Biochem Biophys Res Commun 199:1158–1166

    Article  CAS  PubMed  Google Scholar 

  9. Farooqui AA, Yang H-C, Horrocks LA (1995) Plasmalogens, phospholipases A2 and signal transduction. Brain Res Brain Res Rev 21:152–161

    Article  CAS  PubMed  Google Scholar 

  10. Farooqui AA, Farooqui T, Horrocks LA (2008) Metabolism and functions of bioactive ether lipids. Springer, New York

    Book  Google Scholar 

  11. Bazan NG (2005) Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol 15:159–166

    CAS  PubMed  Google Scholar 

  12. Bazan NG (2009) Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. J Lipid Res 50:S400–S405

    Article  PubMed  CAS  Google Scholar 

  13. Latorre E, Collado MP, Fernández I, Aragonés MD, Catalán RE (2003) Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide. Eur J Biochem 270:36–46

    Article  CAS  PubMed  Google Scholar 

  14. Han X, Holtzman D, Mckeet DW Jr, Kelley J, Morris JC (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis. J Neurochem 82:809–818

    Article  CAS  PubMed  Google Scholar 

  15. Han X (2005) Lipid alterations in the earliest clinically recognizable stage of Alzheimer's disease: implication of the role of lipids in the pathogenesis of Alzheimer's disease. Curr Alzheimer Res 2:65–77

    Article  CAS  PubMed  Google Scholar 

  16. Farooqui AA (2009) Beneficial effects of fish oil on human brain. Springer, New York

    Book  Google Scholar 

  17. Wells K, Farooqui AA, Liss L, Horrocks LA (1995) Neural membrane phospholipids in Alzheimer disease. Neurochem Res 20:1329–1333

    Article  CAS  PubMed  Google Scholar 

  18. Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ (2001) Brain membrane phospholipid alterations in Alzheimer's disease. Neurochem Res 26:771–782

    Article  CAS  PubMed  Google Scholar 

  19. 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

    Article  CAS  PubMed  Google Scholar 

  20. Guan ZZ, Wang YA, Cairns NJ, Lantos PL, Dallner G, Sindelar PJ (1999) Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with Alzheimer disease. J Neuropathol Exp Neurol 58:740–747

    Article  CAS  PubMed  Google Scholar 

  21. Ginsberg L, Xuereb JH, Gershfeld NL (1998) Membrane instability, plasmalogen content, and Alzheimer's disease. J Neurochem 70:2533–2538

    Article  CAS  PubMed  Google Scholar 

  22. Périchon R, Moser AB, Wallace WC, Cunningham SC, Roth GS, Moser HW (1998) Peroxisomal disease cell lines with cellular plasmalogen deficiency have impaired muscarinic cholinergic signal transduction activity and amyloid precursor protein secretion. Biochem Biophys Res Commun 248:57–61

    Article  PubMed  Google Scholar 

  23. Munn NJ, Arnio E, Liu D, Zoeller RA, Liscum L (2003) Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport. J Lipid Res 44:182–192

    Article  CAS  PubMed  Google Scholar 

  24. Goodenowe DB, Cook LL, Liu J, Lu Y, Jayasinghe DA, Ahiahonu PW, Heath D, Yamazaki Y, Flax J, Krenitsky KF, Sparks DL, Lerner A, Friedland RP, Kudo T, Kamino K, Morihara T, Takeda M, Wood PL (2007) Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer's disease and dementia. J Lipid Res 48:2485–2498

    Article  CAS  PubMed  Google Scholar 

  25. Gorgas K, Teigler A, Komljenovic D, Just WW (2006) The ether lipid-deficient mouse: tracking down plasmalogen functions. Biochim Biophys Acta 1763:1511–1526

    Article  CAS  PubMed  Google Scholar 

  26. 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 Brain Res Rev 38:61–78

    Article  CAS  PubMed  Google Scholar 

  27. Farooqui AA (2009) Hot topics in neural membrane lipidology. Springer, New York

    Google Scholar 

  28. Engelmann B, Bräutigam C, Thiery J (1994) Plasmalogen phospholipids as potential protectors against lipid peroxidation of low density lipoproteins. Biochem Biophys Res Commun 204:1235–1242

    Article  CAS  PubMed  Google Scholar 

  29. Maeba R, Ueta N (2004) A novel antioxidant action of ethanolamine plasmalogens in lowering the oxidizability of membranes. Biochem Soc Trans 32:141–143

    Article  CAS  PubMed  Google Scholar 

  30. Zommara M, Tachibana N, Mitsui K, Nakatani N, Sakono M, Ikeda I, Imaizumi K (1995) Inhibitory effect of ethanolamine plasmalogen on iron- and copper-dependent lipid peroxidation. Free Radic Biol Med 18:599–602

    Article  CAS  PubMed  Google Scholar 

  31. Lessig J, Fuchs B (2009) Plasmalogens in biological systems: their role in oxidative processes in biological membranes, their contribution to pathological processes and aging and plasmalogen analysis. Curr Med Chem 16:2021–2041

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Akhlaq A. Farooqui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Farooqui, A.A. Studies on Plasmalogen-Selective Phospholipase A2 in Brain. Mol Neurobiol 41, 267–273 (2010). https://doi.org/10.1007/s12035-009-8091-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-009-8091-y

Keywords

Navigation