期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 30, 页码 10537-10540出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0804852105
关键词
glutamate; neuronal nitric oxide synthase; nitric oxide
资金
- NIDA NIH HHS [DA00074, K05 DA000074] Funding Source: Medline
- NIMH NIH HHS [R37 MH018501-40, R01 MH018501, MH-18501, R37 MH018501, MH079814-01, R01 MH079814, R00 MH079614-03, R00 MH079614] Funding Source: Medline
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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