Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2

Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2
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DOI:
10.1126/science.1119407
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发表时间:
2005-12-23
期刊:
影响因子:
56.9
通讯作者:
Snyder, SH
Snyder, SH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim, SF;Huri, DA;Snyder, SH

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环氧合酶-2(考克斯-2)和诱导型一氧化氮合酶(iNOS)是两种主要的炎症介质。在这里,我们表明,诱导型一氧化氮合酶特异性结合考克斯-2和S-亚硝基化,增强考克斯-2催化活性。选择性破坏iNOS-考克斯-2结合阻止NO介导的考克斯-2活化。两个炎症系统之间的这种协同分子相互作用可能为抗炎药物的开发提供信息。
Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Here we show that iNOS specifically binds to COX-2 and S-nitrosylates it, enhancing COX-2 catalytic activity. Selectively disrupting iNOS-COX-2 binding prevented NO-mediated activation of COX-2. This synergistic molecular interaction between two inflammatory systems may inform the development of anti-inflammatory drugs.