Premium
Matrix metalloproteinase‐2 (MMP‐2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP‐ribose) polymerase (PARP) in vitro
Author(s) -
Kwan Jennifer A.,
Schulze Costas J.,
Wang Wenjie,
Leon Hernando,
Sariahmetoglu Meltem,
Sung Miranda,
Sawicka Jolanta,
Sims David E.,
Sawicki Grzegorz,
Schulz Richard
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1202fje
Subject(s) - poly adp ribose polymerase , matrix metalloproteinase , nuclear matrix , microbiology and biotechnology , parp inhibitor , proteases , nucleus , polymerase , parp1 , myocyte , chemistry , biology , biochemistry , enzyme , dna , chromatin
Matrix metalloproteinases (MMPs) are traditionally known for their role in extracellular matrix remodeling. Increasing evidence reveals several alternative substrates and novel biological roles for these proteases. Recent evidence showed the intracellular localization of MMP‐2 within cardiac myocytes, colocalized with troponin I within myofilaments. Here we investigated the presence of MMP‐2 in the nucleus of cardiac myocytes using both immunogold electron microscopy and biochemical assays with nuclear extracts. The gelatinase activity found in both human heart and rat liver nuclear extracts was blocked with MMP inhibitors. In addition, the ability of MMP‐2 to cleave poly (ADP‐ribose) polymerase (PARP) as a substrate was examined as a possible role for MMP‐2 in the nucleus. PARP is a nuclear matrix enzyme involved in the repair of DNA strand breaks, which is known to be inactivated by proteolytic cleavage. PARP was susceptible to cleavage by MMP‐2 in vitro in a concentration‐dependent manner, yielding novel degradation products of ~66 and <45 kDa. The cleavage of PARP by MMP‐2 was also blocked by MMP inhibitors. This is the first characterization of MMP‐2 within the nucleus and we hereby suggest its possible role in PARP degradation.