Thiol supplementation inhibits metalloproteinase activity independent of glutathione status

Paola Bogani, Monica Canavesi, Tory M. Hagen, Francesco Visioli, Stefano Bellosta

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)651-655
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume363
Issue number3
DOIs
Publication statusPublished - Nov 23 2007

Fingerprint

Metalloproteases
Matrix Metalloproteinases
Sulfhydryl Compounds
Glutathione
Thioctic Acid
Gelatinases
Matrix Metalloproteinase 9
Acetylcysteine
Extracellular Matrix
Reactive Oxygen Species
Antioxidants
Macrophages
Matrix Metalloproteinase 2
Atherosclerosis
Peptide Hydrolases
Chemical activation
Chemical analysis

Keywords

  • Antioxidant
  • Gelatinase
  • Metalloproteinase
  • MMP
  • Reactive oxygen species
  • Thiol

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Thiol supplementation inhibits metalloproteinase activity independent of glutathione status. / Bogani, Paola; Canavesi, Monica; Hagen, Tory M.; Visioli, Francesco; Bellosta, Stefano.

In: Biochemical and Biophysical Research Communications, Vol. 363, No. 3, 23.11.2007, p. 651-655.

Research output: Contribution to journalArticle

Bogani, Paola ; Canavesi, Monica ; Hagen, Tory M. ; Visioli, Francesco ; Bellosta, Stefano. / Thiol supplementation inhibits metalloproteinase activity independent of glutathione status. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 363, No. 3. pp. 651-655.
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