Peroxynitrite inactivates human-tissue inhibitor of metalloproteinase-4
- 作者：S ; ra Donnini ; Martina Monti ; Raffaella Roncone ; Lucia Morbidelli ; Marina Rocchigiani ; Salvatore Oliviero ; Luigi Casella ; Antonio Giachetti ; Richard Schulz ; Marina Ziche
- 关键词：Tissue inhibitor of metalloproteinase-4 ; Peroxynitrite ; Metalloproteinase-2 ; Cell invasiveness ; Nitrative stress
- 刊名：FEBS Letters
- 出版年：2008
- 期刊代码：70_00145793
- 类别：bio
- 出版时间：2 April 2008
- 卷：582
- 期：7
- 页码：1135-1140
- 文件大小：275 K
摘要
Peroxynitrite, via post-translational modifications to target proteins, contributes to cardiovascular injury and cancer. Since tissue inhibitor of metalloproteinase-4 (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.