S-nitrosylation of matrix metalloproteinases: Signaling pathway to neuronal cell death
S-nitrosylation of matrix metalloproteinases: Signaling pathway to neuronal cell death
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DOI：
10.1126/science.1073634
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发表时间：
2002-08-16
期刊：
影响因子：
56.9
通讯作者：
Lipton, SA
中科院分区：
文献类型：
--
作者：
Gu, ZZ;Kaul, M;Lipton, SA
基质金属蛋白酶（MMPs）参与神经退行性疾病和中风的发病机制。然而，MMP激活的机制仍不清楚。我们报告，MMP激活涉及S-亚硝基化。在体内脑缺血期间，MMP-9与神经元型一氧化氮合酶共定位。S-亚硝基化在体外激活MMP-9并诱导神经元凋亡。质谱鉴定MMP-9的活性衍生物，在体外和体内，作为一个稳定的磺酸或磺酸，其形成触发S-亚硝基化。这些研究结果表明，一个潜在的细胞外蛋白水解途径，神经元细胞死亡，S-亚硝基化激活基质金属蛋白酶，并进一步氧化的结果在一个稳定的翻译后修饰与病理活动。
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass spectrometry identified the active derivative of MMP-9, both in vitro and in vivo, as a stable sulfonic or sulfonic acid, whose formation was triggered by S-nitrosylation. These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity.