Neuronal damage by secretory phospholipase A2: modulation by cytosolic phospholipase A2, platelet-activating factor, and cyclooxygenase-2 in neuronal cells in culture
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Neuronal damage by secretory phospholipase A2 : modulation by cytosolic phospholipase A2, platelet-activating factor, and cyclooxygenase-2 in neuronal cells in culture. / Kolko, Miriam; Rodriguez de Turco, Elena B; Diemer, Nils H; Bazan, Nicolas G.
In: Neuroscience Letters, Vol. 338, No. 2, 27.02.2003, p. 164-168.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 128615034