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Inactivation of tissue inhibitor of metalloproteinase‐1 by peroxynitrite
Author(s) -
Frears Emma R.,
Zhang Zhi,
Blake David R.,
O'Connell James P.,
Winyard Paul G.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00065-8
Subject(s) - peroxynitrite , chemistry , in vivo , in vitro , metalloproteinase , fragmentation (computing) , tissue inhibitor of metalloproteinase , biochemistry , connective tissue , matrix metalloproteinase , pharmacology , superoxide , enzyme , biology , ecology , genetics , microbiology and biotechnology
Peroxynitrate (ONOO − ) has recently been implicated in connective tissue destruction in vivo. We have studied the effect of ONOO − on the activity of tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in vitro. The inactivation of TIMP‐1 by ONOO − was dose dependent with 50 μM ONOO − reducing the inhibitory activity of TIMP‐1 towards gelatinase‐A by 50%. High concentrations of ONOO − (500 μM‐5 mM) caused protein fragmentation whilst lower concentrations (<250 μ M) inactivated TIMP‐1 without altering the molecular weight. Inactivation could be blocked by ONOO − scavengers but not by hydroxyl radical scavengers. Our results show that ONOO − is capable of inactivating TIMP‐1, a process which could potentiate metalloproteinase‐mediated tissue breakdown.