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Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10537-40. doi: 10.1073/pnas.0804852105. Epub 2008 Jul 23.

S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity.

Author information

  • 1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

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.

PMID:
18650379
PMCID:
PMC2492460
DOI:
10.1073/pnas.0804852105
[PubMed - indexed for MEDLINE]
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