Secretory phospholipase A2 induces delayed neuronal COX‐2 expression compared with glutamate

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Abstract
Agonists of the binding site for secretory phospholipase A2 (sPLA2) 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 sPLA2. sPLA2-OS2, a selective ligand of a neuronal sPLA2-binding site, was injected into the rat striatum, and early-response gene expression was monitored by in situ hybridization using 35S-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 sPLA2 selectively induced neuronal COX-2; 2) that this induction was delayed (4 hr after injection of sPLA2) 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 sPLA2 may modulate neuronal COX-2 expression through mechanisms that differ from those of glutamate-induced COX-2 expression.

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