Abstract:
:Peroxynitrite (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 microM ONOO- reducing the inhibitory activity of TIMP-1 towards gelatinase-A by 50%. High concentrations of ONOO- (500 microM-5 mM) caused protein fragmentation whilst lower concentrations (<250 microM) 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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Frears ER,Zhang Z,Blake DR,O'Connell JP,Winyard PGdoi
10.1016/0014-5793(96)00065-8subject
Has Abstractpub_date
1996-02-26 00:00:00pages
21-4issue
1-2eissn
0014-5793issn
1873-3468pii
0014-5793(96)00065-8journal_volume
381pub_type
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