Related Experiment Video

Updated: Jun 27, 2026

Using Cell-substrate Impedance and Live Cell Imaging to Measure Real-time Changes in Cellular Adhesion and De-adhesion Induced by Matrix Modification
09:11

Using Cell-substrate Impedance and Live Cell Imaging to Measure Real-time Changes in Cellular Adhesion and De-adhesion Induced by Matrix Modification

Published on: February 19, 2015

Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione

Serena Viappiani1, Adrian C Nicolescu, Andrew Holt

  • 1Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, AB T6G2S2, Canada.

Biochemical Pharmacology
|December 3, 2008
PubMed

Insights

Oxidative stress effector peroxynitrite (ONOO(-)) modulates matrix metalloproteinase-2 (MMP-2) activity. Glutathione (GSH) influences ONOO(-)-mediated MMP-2 regulation, impacting its role in diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Matrix metalloproteinase-2 (MMP-2) is implicated in pathologies linked to oxidative stress.
  • Peroxynitrite (ONOO(-)), a key oxidative stress mediator, is known to activate some MMP zymogens, but its effect on MMP-2 is unclear.
  • Glutathione (GSH) can influence ONOO(-) activity.

Purpose of the Study:

  • To investigate the effect of peroxynitrite (ONOO(-)) on matrix metalloproteinase-2 (MMP-2) zymogen activity.
  • To determine the role of glutathione (GSH) in ONOO(-)-mediated MMP-2 modulation.
  • To elucidate the molecular mechanism of ONOO(-) and GSH interaction with MMP-2.

Main Methods:

  • Treatment of MMP-2 zymogen with varying concentrations of ONOO(-).
  • Enzyme activity assays to measure MMP-2 kinetics (Vmax).
  • Mass spectrometry to analyze ONOO(-) and GSH modifications on MMP-2 and peptides.

Main Results:

  • ONOO(-) exhibited concentration-dependent regulation of MMP-2 activity: low concentrations (0.3-1 microM) increased activity, while high concentrations (30-100 microM) attenuated it.
  • A significant increase in MMP-2 Vmax was observed with 1 microM ONOO(-).
  • ONOO(-) induced oxidation and S-glutathiolation of MMP-2's autoinhibitory domain cysteine residue, a process modulated by GSH.

Conclusions:

  • ONOO(-) and GSH can modulate 72 kDa MMP-2 activity by modifying the cysteine residue in its autoinhibitory domain.
  • These findings suggest a novel regulatory mechanism for MMP-2 relevant to oxidative stress-associated pathophysiological conditions.
  • The dual effect of ONOO(-) on MMP-2 activity highlights the complexity of protease regulation in disease states.

More Related Videos

Alternative Methods for the Detection of Superoxide Anion Generation in Platelets06:35

Alternative Methods for the Detection of Superoxide Anion Generation in Platelets

Published on: March 29, 2024

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation01:22

Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Protein Import into the Peroxisomes01:27

Protein Import into the Peroxisomes

Cells contain membrane-bound organelles called peroxisomes that oxidize organic molecules by transferring hydrogen atoms to oxygen, producing hydrogen peroxide. Peroxisomes enzymatically convert the released hydrogen peroxide into water and oxygen.
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...