Thiol supplementation inhibits metalloproteinase activity independent of glutathione status

Biochem Biophys Res Commun. 2007 Nov 23;363(3):651-5. doi: 10.1016/j.bbrc.2007.09.018. Epub 2007 Sep 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Electrophoresis, Polyacrylamide Gel
  • Glutathione / metabolism*
  • Glutathione / pharmacology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Metalloproteases / antagonists & inhibitors*
  • Metalloproteases / metabolism
  • Sulfhydryl Compounds / pharmacology*
  • Thioctic Acid / pharmacology

Substances

  • Antioxidants
  • Matrix Metalloproteinase Inhibitors
  • Sulfhydryl Compounds
  • Thioctic Acid
  • Metalloproteases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Glutathione
  • Acetylcysteine