Inhibition of matrix metalloproteinase-2 by PARP inhibitors
| Autor: | Pal Pacher, Arulmozhi D. Kandasamy, Andrew Holt, Adrian C. Nicolescu, Richard Schulz |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Matrix metalloproteinase inhibitor
DNA repair Poly ADP ribose polymerase Biophysics Matrix Metalloproteinase Inhibitors Poly(ADP-ribose) Polymerase Inhibitors Matrix metalloproteinase Pharmacology medicine.disease_cause Biochemistry Poly (ADP-Ribose) Polymerase Inhibitor Article Inhibitory Concentration 50 medicine Humans Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Cell Biology Minocycline Phenanthrenes Isoquinolines Molecular biology Zinc Enzyme chemistry Benzamides Oxidative stress medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 387:646-650 |
| ISSN: | 0006-291X |
| Popis: | Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64kDa MMP-2 in a concentration-dependent manner. The IC(50) values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect