S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity |
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| Authors: | Tian Jing Kim Sangwon F Hester Lynda Snyder Solomon H |
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| Institution: | Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA. |
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| 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. |
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| Keywords: | glutamate neuronal nitric oxide synthase nitric oxide |
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