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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)10537-10540
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number30
DOIs
StatePublished - Jul 29 2008

Keywords

  • Glutamate
  • Neuronal nitric oxide synthase
  • Nitric oxide

ASJC Scopus subject areas

  • General

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