Inhibition of matrix metalloproteinase-2 by PARP inhibitors.

ABSTRACT: 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-phena

SUBMITTER: Nicolescu AC 

PROVIDER: S-EPMC2756481 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature