S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity
- 29 July 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (30) , 10537-10540
- https://doi.org/10.1073/pnas.0804852105
Abstract
Glutamate/N-methyl-d-aspartate (NMDA) receptor-mediated neurotoxicity involves cyclooxygenase (COX)-2. We demonstrate that this neurotoxicity reflects activation of COX-2 byS-nitrosylation after selective binding of neuronal nitric oxide synthase (nNOS) to COX-2. nNOS, via its PDZ domain, binds COX-2 with the generated NOS-nitrosylating and activating the enzyme. Selective disruption of nNOS—COX-2 binding prevents NMDA neurotoxicity.Keywords
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