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

Jing Tian; Sangwon F. Kim; Lynda Hester; Solomon H. Snyder

doi:10.1073/pnas.0804852105

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

Jing Tian, Sangwon F. Kim, Lynda Hester, Solomon H. Snyder

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

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 language	English (US)
Pages (from-to)	10537-10540
Number of pages	4
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	30
DOIs	https://doi.org/10.1073/pnas.0804852105
State	Published - Jul 29 2008
Externally published	Yes

Keywords

Glutamate
Neuronal nitric oxide synthase
Nitric oxide

ASJC Scopus subject areas

General

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10.1073/pnas.0804852105

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title = "S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity",

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.",

keywords = "Glutamate, Neuronal nitric oxide synthase, Nitric oxide",

author = "Jing Tian and Kim, {Sangwon F.} and Lynda Hester and Snyder, {Solomon H.}",

year = "2008",

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doi = "10.1073/pnas.0804852105",

language = "English (US)",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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T1 - S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity

AU - Tian, Jing

AU - Kim, Sangwon F.

AU - Hester, Lynda

AU - Snyder, Solomon H.

PY - 2008/7/29

Y1 - 2008/7/29

N2 - 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.

AB - 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.

KW - Glutamate

KW - Neuronal nitric oxide synthase

KW - Nitric oxide

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DO - 10.1073/pnas.0804852105

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AN - SCOPUS:48749087958

SN - 0027-8424

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

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

Abstract

Keywords

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