Neuronal damage by secretory phospholipase A2: modulation by cytosolic phospholipase A2, platelet-activating factor, and cyclooxygenase-2 in neuronal cells in culture
Research output: Contribution to journal › Journal article › Research › peer-review
Activation of cytosolic phospholipase A(2) (cPLA(2)) is an early event in brain injury, which leads to the formation and accumulation of bioactive lipids: platelet-activating factor (PAF), free arachidonic acid, and eicosanoids. A cross-talk between secretory PLA(2) (sPLA(2)) and cPLA(2) in neural signal transduction has previously been suggested (J Biol Chem 271:32722; 1996). Here we show, using neuronal cell cultures, an up-regulation of cPLA(2) expression and an inhibition by the selective cPLA(2) inhibitor AACOCF3 after exposure to neurotoxic concentrations of sPLA(2)-OS2. Pretreatment of neuronal cultures with recombinant PAF acetylhydrolase (rPAF-AH) or the presynaptic PAF receptor antagonist, BN52021, partially blocked neuronal cell death induced by sPLA(2)-OS2. Furthermore, selective COX-2 inhibitors ameliorated sPLA(2)-OS2-induced neurotoxicity. We conclude that sPLA(2)-OS2 activates a neuronal signaling cascade that includes activation of cPLA(2), arachidonic acid release, PAF production, and induction of COX-2.
|Number of pages||5|
|Publication status||Published - 27 Feb 2003|
- 1-Alkyl-2-acetylglycerophosphocholine Esterase, Animals, Arachidonic Acids, Cell Death, Cells, Cultured, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Cytosol, Diterpenes, Embryo, Mammalian, Enzyme Induction, Ginkgolides, Isoenzymes, L-Lactate Dehydrogenase, Lactones, Neurons, Neurotoxins, Phospholipases A, Phospholipases A2, Platelet Activating Factor, Platelet Membrane Glycoproteins, Prostaglandin-Endoperoxide Synthases, Rats, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Recombinant Proteins, Reptilian Proteins, Up-Regulation