Cyclooxygenase-2 contributes to VX-induced cell death in cultured cortical neurons.
The link between cell death and increased cyclooxygenases-2 (COX-2) activity has not been clearly established. In this study, we examined whether COX-2 activation contributed to the mechanism of neurotoxicity produced by an organophosphorous nerve agent in cultured rat cortical neurons. Exposure of neuronal cells to the nerve agent, VX resulted in an increase in COX enzyme activity in the culture media. A concentration dependent increase in the activity levels of COX-2 enzyme was observed while there was little to no effect on COX-1. In addition, COX-2 mRNA and protein levels increased several hours post-VX exposure. Pre-treatment of the cortical cells with the COX-2 selective inhibitor, NS 398 resulted in a decrease in both the enzyme activity and prostaglandin (PGE(2) and PGF(2α)) release, as well as in a reduction in cell death. These findings indicate that the increase in COX-2 activity may contribute to the mechanism of VX-induced neurotoxicity in cultured rat cortical neuron.
DRDC Suffield, Station Main, Medicine Hat, Alberta, Canada. catherine.tenn@drdc-rddc.gc.ca
Catherine C
CC
Tenn
M Tracy
MT
Weiss
Claire
C
Beaup
Andre
A
Peinnequin
Yushan
Y
Wang
Frederic
F
Dorandeu
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000502:physiology*; D015237:Dinoprost / Q000032:analysis; D015232:Dinoprostone / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
D002800:Cholinesterase Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015237:Dinoprost; D015232:Dinoprostone; D009946:Organothiophosphorus Compounds; C009680:VX-agent