TY - JOUR

T1 - Neuronal damage by secretory phospholipase A2

T2 - modulation by cytosolic phospholipase A2, platelet-activating factor, and cyclooxygenase-2 in neuronal cells in culture

AU - Kolko, Miriam

AU - Rodriguez de Turco, Elena B

AU - Diemer, Nils H

AU - Bazan, Nicolas G

PY - 2003/2/27

Y1 - 2003/2/27

N2 - 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.

AB - 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.

KW - 1-Alkyl-2-acetylglycerophosphocholine Esterase

KW - Animals

KW - Arachidonic Acids

KW - Cell Death

KW - Cells, Cultured

KW - Cyclooxygenase 2

KW - Cyclooxygenase 2 Inhibitors

KW - Cyclooxygenase Inhibitors

KW - Cytosol

KW - Diterpenes

KW - Embryo, Mammalian

KW - Enzyme Induction

KW - Ginkgolides

KW - Isoenzymes

KW - L-Lactate Dehydrogenase

KW - Lactones

KW - Neurons

KW - Neurotoxins

KW - Phospholipases A

KW - Phospholipases A2

KW - Platelet Activating Factor

KW - Platelet Membrane Glycoproteins

KW - Prostaglandin-Endoperoxide Synthases

KW - Rats

KW - Receptors, Cell Surface

KW - Receptors, G-Protein-Coupled

KW - Recombinant Proteins

KW - Reptilian Proteins

KW - Up-Regulation

U2 - 10.1016/S0304-3940(02)01385-X

DO - 10.1016/S0304-3940(02)01385-X

M3 - Journal article

C2 - 12566178

VL - 338

SP - 164

EP - 168

JO - Neuroscience letters. Supplement

JF - Neuroscience letters. Supplement

SN - 0167-6253

IS - 2

ER -