S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity
S-nitrosylation/activation of COX-2 mediates NMDA neurotoxicity
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DOI：
10.1073/pnas.0804852105
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发表时间：
2008-07-29
影响因子：
11.1
通讯作者：
Snyder, Solomon H.
中科院分区：
文献类型：
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作者：
Tian, Jing;Kim, Sangwon F.;Snyder, Solomon H.
谷氨酸/N-甲基-D-天冬氨酸（NMDA）受体介导的神经毒性涉及环氧合酶（考克斯）-2。我们证明，这种神经毒性反映了神经元型一氧化氮合酶（nNOS）选择性结合后，S-亚硝基化激活考克斯-2的考克斯-2。nNOS通过其PDZ结构域与考克斯-2结合，产生NOS-亚硝基化并激活酶。选择性破坏nNOS-COX-2结合可防止NMDA神经毒性。
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.