期刊
SCIENCE
卷 297, 期 5584, 页码 1186-1190出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1073634
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资金
- NCI NIH HHS [R01 CA 69306] Funding Source: Medline
- NEI NIH HHS [R01 EY09024, R01 EY05477] Funding Source: Medline
- NIAMS NIH HHS [AR08505, R01 AR42750] Funding Source: Medline
- NIA NIH HHS [T32 AG00252] Funding Source: Medline
- NICHD NIH HHS [P01 HD29587] Funding Source: Medline
- NINDS NIH HHS [R01 NS41207] Funding Source: Medline
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.
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