Thiol supplementation inhibits metalloproteinase activity independent of glutathione status
Related Experiment Video
Updated: Jul 11, 2026

Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
Paola Bogani1, Monica Canavesi, Tory M Hagen
1Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Abstract:
Matrix metalloproteinases (MMPs) are proteolytic enzymes that regulate both integrity and composition of the extracellular matrix (ECM). Excessive ECM breakdown by MMPs is implicated in many physiological and pathological conditions, such as atherosclerosis. Activated macrophages, especially in the atherosclerotic lesion, are a major source of reactive oxygen species (ROS). Antioxidants protect against ROS-induced MMPs activation and inhibit gelatinolytic activity. We sought to determine whether the antioxidants glutathione (GSH), N-acetylcysteine (NAC), or lipoic acid (LA) affect gelatinase production and secretion. The results show that thiol compounds affect MMPs expression and activity in different ways. MMP-2 activity is directly inhibited by NAC and GSH, while LA is ineffective. On the contrary, MMP-9 expression is inhibited by LA at a pretrascriptional level, and MMP-9 activity is stimulated by GSH through a direct interaction with the gelatinase itself. Although all thiols, these compounds have different properties and different cellular uptakes and metabolic characteristics, and this could explain, at least in part, their differential effects on MMPs.
Insights
Antioxidants like glutathione (GSH), N-acetylcysteine (NAC), and lipoic acid (LA) differentially impact matrix metalloproteinases (MMPs). These compounds affect MMP-2 and MMP-9 expression and activity, crucial in conditions like atherosclerosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Matrix metalloproteinases (MMPs) are enzymes regulating extracellular matrix (ECM) integrity.
- Excessive ECM degradation by MMPs contributes to diseases like atherosclerosis.
- Activated macrophages in atherosclerotic lesions produce reactive oxygen species (ROS), influencing MMPs.
Purpose of the Study:
- To investigate the effects of antioxidants glutathione (GSH), N-acetylcysteine (NAC), and lipoic acid (LA) on gelatinase production and secretion.
- To understand the differential impact of thiol compounds on MMP expression and activity.
Main Methods:
- Assessing the influence of GSH, NAC, and LA on MMP-2 and MMP-9 activity.
- Investigating the pre-transcriptional and direct interaction effects of these antioxidants on MMPs.
Main Results:
- NAC and GSH directly inhibited MMP-2 activity; LA was ineffective.
- LA inhibited MMP-9 expression at a pre-transcriptional level.
- GSH directly stimulated MMP-9 activity via interaction with the enzyme.
Conclusions:
- Thiol compounds exhibit varied effects on MMPs due to differing properties, cellular uptake, and metabolic characteristics.
- These differential effects provide insights into managing MMPs in pathological conditions like atherosclerosis.
More Related Videos
11:04Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
Published on: September 7, 2019
09:51Standards for Quantitative Metalloproteomic Analysis Using Size Exclusion ICP-MS
Published on: April 13, 2016
Related Concept Videos
Preparation and Reactions of Thiols
Sulfur Assimilation
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Antiprotozoal Agents
Role of Matrix Metalloproteases in Degradation of ECM
A...