Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate.
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.
Laboratory of Neuropathology, University of Copenhagen, Copenhagen, Denmark.
Miriam
M
Kolko
Marianne
M
Nielsen
Nicolas G
NG
Bazan
Nils H
NH
Diemer
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016762:Genes, fos; D016758:Genes, jun; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D009474:Neurons / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation
D007527:Isoenzymes; D008565:Membrane Proteins; D018698:Glutamic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D010741:Phospholipases A