title: 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.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kwan
authors.forename: Costas J
authors.initials: CJ
authors.lastname: Schulze
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.forename: Hernando
authors.initials: H
authors.lastname: Leon
authors.forename: Meltem
authors.initials: M
authors.lastname: Sariahmetoglu
authors.forename: Miranda
authors.initials: M
authors.lastname: Sung
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sawicka
authors.forename: David E
authors.initials: DE
authors.lastname: Sims
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Sawicki
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000201:enzymology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats
chemical_list: D011065:Poly(ADP-ribose) Polymerases; D020778:Matrix Metalloproteinase 2