Cellular and Molecular Neurobiology

, Volume 25, Issue 7, pp 1107–1122 | Cite as

Expression and Induction of Secretory Phospholipase A Group IB in Brain

  • Miriam Kolko
  • Nanna R. Christoffersen
  • Hélène Varoqui
  • Nicolas G. Bazan1
Original Research


Secretory phospholipases A2 (sPLA2) form a diverse family of enzymes involved in physiologicand pathologic processes. Common among all sPLA2 is the ability to cleave acyl groups of phospholipids at 2C of the glycerol backbone, thereby releasingfatty acid and a lysophospholipid. Several sPLA2 have been cloned and characterized in various tissues.Furthermore, receptors have been identified. In the nervous system sPLA2 groups IIA, IIE, IIF, V, and XII have been identified, and binding sites for sPLA2 group IB (sPLA2-IB) have been found. Here, we report sPLA2-IB in rat and human brain as well as in neurons in primary culture. The distribution of sPLA2-IB seems to be mainly neuronal, with the highest abundance occurring in the cerebral cortex and hippocampus. We also find that genes encoding sPLA2-IB are induced by kainic acid and by electroshock-induced convulsions.Based on the present results we suggest that sPLA2-IB may be a neuronal intercellular signalling modulator.

Key Words

secretory phospholipase A2 group IB neuronal expression seizure epilepsy gene induction 



arachidonic acid




open reading frame


reverse transcription-polymerase chain reaction


secreted phospholipase A2


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  1. Balboa, M. A., Varela-Nieto, I., Lucas, K. K., and Dennis, E. A. (2002). Expression and function of phospholipase A2 in brain. FEBS Lett. 531:12–17.CrossRefPubMedGoogle Scholar
  2. Baran, H., Vass, K., Lassmann, H., and Hornykiewicz, O. (1994). The cyclooxygenase and lipoxygenase inhibitor BW755C protects rats against kainic acid-induced seizures and neurotoxicity. Brain Res. 646:201–206.CrossRefPubMedGoogle Scholar
  3. Bazan, N. G. (2003). Synaptic lipid signalling: significance of polyunsaturated fatty acids and platelet-activating factor. J. Lipid Res. 44:2221–2233.PubMedGoogle Scholar
  4. Chen, J., Engle, S. J., Seilhamer, J. J., and Tischfield, J. A. (1994). Cloning, expression and partial characterization of a novel rat phospholipase A2. Biochim. Biophys. Acta. 1215:115–120.PubMedGoogle Scholar
  5. Chen, M., Yang, Z., Naji, A., and Wolf, B. A. (1996). Identification of calcium-dependent phospholipase A2 isoforms in human and rat pancreatic islets and insulin secreting beta-cell lines. Endocrinology 137:2901–2909.PubMedGoogle Scholar
  6. Copic, A., Vucemilo, N., Gubensek, F., and Krizaj, I. (1999). Identification and purification of a novel receptor for secretory phospholipase A(2) in porcine cerebral cortex. J. Biol. Chem. 274:26315–26320.CrossRefPubMedGoogle Scholar
  7. Cupillard, L., Mulherkar, R., Gomez, N., Kadam, S., Valentin, E., Lazdunski, M., and Lambeau, G. (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.CrossRefPubMedGoogle Scholar
  8. DeCoster, M. A., and Yourick, D. L. (1994). Development of glutamate-stimulated phosphatidylinositol metabolism in primary neuronal and astrocyte cultures. Int. J. Dev. Neurosci. 12:227–233.PubMedCrossRefGoogle Scholar
  9. Hanasaki, K., and Arita, H. (1992). Characterization of a high affinity binding site for pancreatic-type phospholipase A2 in the rat. Its cellular and tissue distribution. J. Biol. Chem. 267:6414–6420.PubMedGoogle Scholar
  10. Hanasaki, K., and Arita, H. (1999). Biological and pathological functions of phospholipase A(2) receptor. Arch. Biochem. Biophys. 372:215–223.CrossRefPubMedGoogle Scholar
  11. Hanasaki, K., and Arita, H. (2002). Phospholipase A2 receptor: A regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Mediat. 68–69:71–82.PubMedGoogle Scholar
  12. Horrocks, L. A., and Farooqui, A. A. (1994). NMDA receptor-stimulated release of arachidonic acid: Mechanisms for the Bazan effect. In: Municio, A. M., and Miras-Portugal, M. T. (eds.), Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease. Plenum Press, New York, NY, pp. 113–128.Google Scholar
  13. Kolko, M., DeCoster, M. A., Rodriguez de Turco, E. B., and Bazan, N. G. (1996). Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures. J. Biol. Chem. 271:32722–32728.PubMedGoogle Scholar
  14. Kolko, M., Nielsen, M., Bazan, N. G., and Diemer, N. H. (2002). Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate. J. Neurosci. Res. 69:169–177.CrossRefPubMedGoogle Scholar
  15. Kolko, M., Rodriguez de Turco, E. B., Diemer, N. H., and Bazan, N. G. (2003). Neuronal damage by secretory phospholipase A2: modulation by cytosolic phospholipase A2, platelet-activating factor, and cyclooxygenase-2 in neuronal cells in culture. Neurosci. Lett. 338:164–168.CrossRefPubMedGoogle Scholar
  16. Kolko, M., Christoffersen, N. R., Barreiro, S. G., and Bazan, N. G. (2004). Expression and location of mRNAs encoding multiple forms of secretory phospholipase A2 in the rat retina. J. Neurosci. Res. 77:517–524.CrossRefPubMedGoogle Scholar
  17. Kudo, I., and Murakami, M. (2002). Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 68–69:3–58.PubMedGoogle Scholar
  18. Marcheselli, V. L., and Bazan, N. G. (1996). Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus. Inhibition by a platelet-activating factor antagonist. J. Biol. Chem. 271:24794–24799.PubMedGoogle Scholar
  19. Marcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X., Gronert, K., Musto, A., Hardy, M., Gimenez, J. M., Chiang, N., Serhan, C. N., and Bazan, N. G. (2003). Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J. Biol. Chem. 278:43908–43817.CrossRefGoogle Scholar
  20. Molloy, G. Y., Rattray, M., and Williams, R. J. (1998). Genes encoding multiple forms of phospholipase A2 are expressed in rat brain. Neurosci. Lett. 258:139–142.CrossRefPubMedGoogle Scholar
  21. Ohara, O., Tamaki, M., Nakamura, E., Tsuruta, Y., Fujii, Y., Shin, M., Teraoka, H., and Okamoto, M. (1986). Dog and rat pancreatic phospholipases A2: complete amino acid sequences deduced from complementary DNAs. J. Biochem. (Tokyo) 99:733–739.Google Scholar
  22. Six, D. A., and Dennis, E. (2000). The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochim. Biophys. Acta. 1488:1–19.PubMedGoogle Scholar
  23. Sribar, J., Copic, A., Paris, A., Sherman, N. E., Gubensek, F., Fox, J. W., and Krizaj, I. (2001). A high affinity acceptor for phospholipase A2 with neurotoxic activity is a calmodulin. J. Biol. Chem. 276:12493–12496.CrossRefPubMedGoogle Scholar
  24. Sun, G. Y., Xu, J., Jensen, M. D., and Simonyi, A. (2004). Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J. Lipid Res. 45:205–213.PubMedGoogle Scholar
  25. Valentin, E., and Lambeau, G. (2000a). What can venom phospholipases A(2) tell us about the functional diversity of mammalian secreted phospholipases A(2)? Biochimie. 82:815–831.CrossRefGoogle Scholar
  26. Valentin, E., and Lambeau, G. (2000b). Increasing molecular diversity of secreted phospholipases A(2) and their receptors and binding proteins. Biochim. Biophys. Acta 1488:59–70.Google Scholar
  27. Valentin, E., Ghomashchi, F., Gelb, M. H., Lazdunski, M., and Lambeau, G. (1999). On the diversity of secreted phospholipases A(2). Cloning, tissue distribution, and functional expression of two novel mouse group II enzymes. J. Biol. Chem. 274:31195–311202.PubMedGoogle Scholar
  28. Yagami, T., Ueda, K., Asakura, K., Hata, S., Kuroda, T., Sakaeda, T., Kishino, J., Sakaguchi, G., Itoh, N., and Hori, Y. (2002a). Group IB secretory phospholipase A(2)induces cell death in the cultured cortical neurons: a possible involvement of its binding sites. Brain Res. 949:197–201.CrossRefGoogle Scholar
  29. Yagami, T., Ueda, K., Asakura, K., Hayasaki-Kajiwara, Y., Nakazato, H., Sakaeda, T., Hata, S., Kuroda, T., Takasu, N. and Hori, Y. (2002b). Group IB secretory phospholipase A2 induces neuronal cell death via apoptosis. J. Neurochem. 81:449–461.CrossRefGoogle Scholar
  30. Yagami, T., Ueda, K., Asakura, K., Sakaeda, T., Hata, S., Kuroda, T., Sakaguchi, G., Itoh, N., Hashimoto, Y., and Hori, Y. (2003). Porcine pancreatic group IB secretory phospholipase A2 potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels. Brain Res. 960:71–80.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Miriam Kolko
    • 1
    • 2
  • Nanna R. Christoffersen
    • 1
  • Hélène Varoqui
    • 1
  • Nicolas G. Bazan1
    • 1
    • 3
  1. 1.Neuroscience Center of Excellence and Department of OphthalmologyLouisiana State University Health Sciences Center School of MedicineNew Orleans
  2. 2.Present address: Eye Pathology InstituteUniversity of CopenhagenDenmark
  3. 3.LSU Neuroscience Center of ExcellenceNew Orleans

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