Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate

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Miriam Kolko, Marianne Nielsen, Nicolas G Bazan, Nils H Diemer, Miriam Kolko

Agonists of the binding site for secretory phospholipase A(2) (sPLA(2)) potentiate glutamate-induced neuronal cell death in primary cell cultures and in vivo (Kolko et al. [1996] J. Biol. Chem. 271:32722; Kolko et al. [1999] Neurosci. Lett. 274:167]. Here, we tested the hypothesis that COX-2 expression participates in the brain response to sPLA(2). sPLA(2)-OS(2), a selective ligand of a neuronal sPLA(2)-binding site, was injected into the rat striatum, and early-response gene expression was monitored by in situ hybridization using (35)S-radiolabeled oligonucleotide probes and immunohistochemistry. An up-regulation of COX-2, c-fos, and c-jun, but not COX-1, was observed around the lesion as well as in the neocortex 4 hr after the injection. Hippocampal up-regulation of COX-2 was seen in dentate gyrus 8 hr after injection. When glutamate was injected, up-regulation of the early-response genes peaked after 2 hr. Our studies showed 1) that sPLA(2) selectively induced neuronal COX-2; 2) that this induction was delayed (4 hr after injection of sPLA(2)) compared with that elicited by glutamate (2 hr after injection), suggesting different signaling; and 3) that c-fos and c-jun were induced around the infarct area as soon as 2 hr after injection, but in other aspects followed a time course similar to that of COX-2. We conclude that sPLA(2) may modulate neuronal COX-2 expression through mechanisms that differ from those of glutamate-induced COX-2 expression.

Original languageEnglish
JournalJournal of Neuroscience Research
Volume69
Issue number2
Pages (from-to)169-77
Number of pages9
ISSN0360-4012
DOIs
Publication statusPublished - 15 Jul 2002

    Research areas

  • Animals, Corpus Striatum, Cyclooxygenase 1, Cyclooxygenase 2, Genes, fos, Genes, jun, Glutamic Acid, Immunohistochemistry, In Situ Hybridization, Isoenzymes, Male, Membrane Proteins, Neurons, Phospholipases A, Prostaglandin-Endoperoxide Synthases, Rats, Rats, Wistar, Time Factors, Up-Regulation

ID: 128614405