Abstract
Glutamate/N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity involves cyclooxygenase (COX)-2. We demonstrate that this neurotoxicity reflects activation of COX-2 by S-nitrosylation after selective binding of neuronal nitric oxide synthase (nNOS) to COX-2. nNOS, via its PDZ domain, binds COX-2 with the generated NO S-nitrosylating and activating the enzyme. Selective disruption of nNOS - COX-2 binding prevents NMDA neurotoxicity.
Original language | English (US) |
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Pages (from-to) | 10537-10540 |
Number of pages | 4 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 105 |
Issue number | 30 |
DOIs | |
State | Published - Jul 29 2008 |
Externally published | Yes |
Keywords
- Glutamate
- Neuronal nitric oxide synthase
- Nitric oxide
ASJC Scopus subject areas
- General