Inactivation of tissue inhibitor of metalloproteinase‐1 by peroxynitrite

FEBS Letters

Blake, David R.¹  Winyard, Paul G.¹  O'Connell, James P.²  Zhang, Zhi¹  Frears, Emma R.¹ 

[1]The Inflammation Research Group, London Hospital Medical College, University of London, London E1 2AD, UK

[2]Celltech Limited, 216 Bath Road, Slough, SL1 4EN, UK

关键词: Tissue inhibitor of metalloproteinases;    Peroxynitrite;    Nitric oxide;    Reactive nitrogen species;    Inflammation;    Reactive oxygen species;    Connective tissue damage;    TIMP;    tissue inhibitor of metalloproteinases;    APMA;    (4-aminophenyl) mercuric acid;    SDS-PAGE;    sodium dodecyl sulphate polyacrylamide gel electrophoresis;   

DOI  :  10.1016/0014-5793(96)00065-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM) 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.

【 授权许可】

Unknown