Abstract
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.
| Original language | English |
|---|---|
| Journal | Neuroscience Letters |
| Volume | 338 |
| Issue number | 2 |
| Pages (from-to) | 164-8 |
| Number of pages | 5 |
| ISSN | 0304-3940 |
| Publication status | Published - 27 Feb 2003 |
Keywords
- 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