TY - JOUR

T1 - Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate

AU - Kolko, Miriam

AU - Nielsen, Marianne

AU - Bazan, Nicolas G

AU - Diemer, Nils H

N1 - Copyright 2002 Wiley-Liss, Inc.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Animals

KW - Corpus Striatum

KW - Cyclooxygenase 1

KW - Cyclooxygenase 2

KW - Genes, fos

KW - Genes, jun

KW - Glutamic Acid

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Isoenzymes

KW - Male

KW - Membrane Proteins

KW - Neurons

KW - Phospholipases A

KW - Prostaglandin-Endoperoxide Synthases

KW - Rats

KW - Rats, Wistar

KW - Time Factors

KW - Up-Regulation

U2 - 10.1002/jnr.10288

DO - 10.1002/jnr.10288

M3 - Journal article

C2 - 12111798

VL - 69

SP - 169

EP - 177

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 2

ER -