Inactivation of tissue inhibitor of metalloproteinase-1 by peroxynitrite.

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 Lett

journal_title

FEBS letters

authors

Frears ER,Zhang Z,Blake DR,O'Connell JP,Winyard PG

doi

10.1016/0014-5793(96)00065-8

subject

Has Abstract

pub_date

1996-02-26 00:00:00

pages

21-4

issue

1-2

eissn

0014-5793

issn

1873-3468

pii

0014-5793(96)00065-8

journal_volume

381

pub_type

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