S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity.
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.
Mesh Terms:
Animals, Biotin, Brain, Cell Death, Cerebellum, Cyclooxygenase 2, Enzyme Activation, Humans, Membrane Proteins, Mice, N-Methylaspartate, Neurons, Nitric Oxide Synthase Type II, Protein Binding, Receptors, N-Methyl-D-Aspartate
Animals, Biotin, Brain, Cell Death, Cerebellum, Cyclooxygenase 2, Enzyme Activation, Humans, Membrane Proteins, Mice, N-Methylaspartate, Neurons, Nitric Oxide Synthase Type II, Protein Binding, Receptors, N-Methyl-D-Aspartate
Proc. Natl. Acad. Sci. U.S.A.
Date: Jul. 29, 2008
PubMed ID: 18650379
View in: Pubmed Google Scholar
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