Peroxynitrite inactivates human‐tissue inhibitor of metalloproteinase‐4
Copyright policy )Peroxynitrite inactivates human‐tissue inhibitor of metalloproteinase‐4
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.
- University of Alberta Canada
- University of Pavia Italy
- University of Siena Italy
- University of Turin Italy
570, Cell invasiveness; Metalloproteinase-2; Nitrative stress; Peroxynitrite; Tissue inhibitor of metalloproteinase-4, 610, Peroxynitrite, Cell Movement, Cell Line, Tumor, Peroxynitrous Acid, Animals, Humans, Cells, Cultured, Tissue Inhibitor of Metalloproteinase-4, Tissue Inhibitor of Metalloproteinases, Nitrative stre, PEROXYNITRITE, Cell invasiveness, Tissue inhibitor of metalloproteinase-4, Cell invasivene, Tyrosine, Cattle, METALLOPROTEINASE, Endothelium, Vascular, Metalloproteinase-2, INHIBITORS, Nitrative stress
570, Cell invasiveness; Metalloproteinase-2; Nitrative stress; Peroxynitrite; Tissue inhibitor of metalloproteinase-4, 610, Peroxynitrite, Cell Movement, Cell Line, Tumor, Peroxynitrous Acid, Animals, Humans, Cells, Cultured, Tissue Inhibitor of Metalloproteinase-4, Tissue Inhibitor of Metalloproteinases, Nitrative stre, PEROXYNITRITE, Cell invasiveness, Tissue inhibitor of metalloproteinase-4, Cell invasivene, Tyrosine, Cattle, METALLOPROTEINASE, Endothelium, Vascular, Metalloproteinase-2, INHIBITORS, Nitrative stress
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