Inactivation of tissue inhibitor of metalloproteinase-1 by peroxynitrite

FEBS Lett. 1996 Feb 26;381(1-2):21-4. doi: 10.1016/0014-5793(96)00065-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Free Radical Scavengers / pharmacology
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / isolation & purification
  • Glycoproteins / pharmacology*
  • Humans
  • Kinetics
  • Matrix Metalloproteinase 3
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / metabolism*
  • Molecular Sequence Data
  • Nitrates / chemical synthesis
  • Nitrates / pharmacology*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Substrate Specificity
  • Tissue Inhibitor of Metalloproteinases

Substances

  • Amino Acids
  • Free Radical Scavengers
  • Glycoproteins
  • Nitrates
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinases
  • peroxynitric acid
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3