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

نویسندگان

  • Jing Tian
  • Sangwon F Kim
  • Lynda Hester
  • Solomon H Snyder
چکیده

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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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 105 30  شماره 

صفحات  -

تاریخ انتشار 2008