Peroxynitrite inactivates human-tissue inhibitor of metalloproteinase-4
Peroxynitrite inactivates human-tissue inhibitor of metalloproteinase-4
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DOI：
10.1016/j.febslet.2008.02.080
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发表时间：
2008-04-02
期刊：
影响因子：
3.5
通讯作者：
Ziche, Marina
中科院分区：
文献类型：
--
作者：
Donnini, Sandra;Monti, Martina;Ziche, Marina
过氧亚硝酸盐通过靶蛋白的翻译后修饰导致心血管损伤和癌症。由于在两种病理条件下活性受损的组织金属蛋白酶4 （TIMP-4）具有几个对过氧亚硝酸盐敏感的氨基酸残基，因此我们研究了其作为过氧亚硝酸盐潜在靶点的作用。过氧亚硝酸盐诱导的TIMP-4的硝化和寡聚化降低了其对MMP-2活性和内皮细胞或肿瘤细胞侵袭性的抑制活性。此外，过氧亚硝酸盐处理细胞促进内源性TIMP-4的硝化。HPLC/ESI-MS/MS分析显示，经过氧亚硝酸盐处理的TIMP-4在Y114、Y195、Y188和Y190位点发生修饰。综上所述，TIMP-4硝化可能是导致心血管疾病和癌症的潜在机制。(C) 2008年欧洲生化学会联合会。Elsevier B.V.版权所有。
Peroxynitrite, via post-translational modifications to target proteins, contributes to cardiovascular injury and cancer. Since tissue inhibitor of metalloproteinase4 (TIMP-4), the activity of which is impaired in both pathological conditions, has several amino acid residues susceptible to peroxynitrite, we investigated its role as a potential target of peroxynitrite. Peroxynitrite-induced nitration and oligomerization of TIMP-4 attenuated its inhibitory activity against MMP-2 activity and endothelial or tumor cell invasiveness. Moreover, cell treatment with peroxynitrite promoted the nitration of endogenous TIMP-4. HPLC/ESI-MS/MS analysis of peroxynitrite-treated TIMP-4 showed modifications at Y114, Y195, Y188 and Y190. In conclusion, TIMP-4 nitration might be a potential mechanism contributing to cardiovascular disease and cancer. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.