Document Detail

Zinc protects endothelial cells from hydrogen peroxide via Nrf2-dependent stimulation of glutathione biosynthesis.
MedLine Citation:
PMID:  18355458     Owner:  NLM     Status:  MEDLINE    
Oxidative stress is one of the main causes of vascular disease. This study aims to investigate the antioxidant activity exerted by zinc in primary rat endothelial cells (EC). Using a 24-h treatment with hydrogen peroxide as a model for oxidative stress, we found that zinc supplementation protects from peroxide-induced cell death via increasing the transcription of the catalytic subunit (heavy chain) of glutamate-cysteine ligase (GCLC) and the concentrations of glutathione (GSH). Conversely, zinc depletion significantly decreased the expression of GCLC and the cellular GSH levels, resulting in an increased susceptibility of EC to oxidative stress. Using confocal microscopy and the RNA silencing technique, we found that zinc upregulates the expression of GCLC by activating the transcription factor Nrf2. Surprisingly, the intracellular zinc sensor, metal-responsive transcription factor-1, is not involved in the zinc-induced expression of GCLC. The present study shows that zinc controls the redox state of EC by regulating the de novo synthesis of GSH. This molecular mechanism may contribute to the elaboration of new nutritional and/or pharmaceutical approaches for protecting the endothelium against oxidative stress.
Miriam M Cortese; Christoph V Suschek; Wiebke Wetzel; Klaus-D Kröncke; Victoria Kolb-Bachofen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-08
Journal Detail:
Title:  Free radical biology & medicine     Volume:  44     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-26     Completed Date:  2008-09-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2002-12     Citation Subset:  IM    
Institute of Molecular Medicine, Research Group Immunobiology, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
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MeSH Terms
Cells, Cultured
DNA-Binding Proteins / metabolism
Endothelial Cells / metabolism*
Endothelium, Vascular / metabolism
Glutamate-Cysteine Ligase / biosynthesis*
Glutathione / biosynthesis*
Hydrogen Peroxide / pharmacology*
NF-E2-Related Factor 2 / metabolism*
Oxidative Stress
Transcription Factors / metabolism
Zinc / physiology*
Zinc Sulfate / pharmacology
Reg. No./Substance:
0/DNA-Binding Proteins; 0/NF-E2-Related Factor 2; 0/Nfe2l2 protein, rat; 0/Transcription Factors; 0/transcription factor MTF-1; 70-18-8/Glutathione; 7440-66-6/Zinc; 7722-84-1/Hydrogen Peroxide; 7733-02-0/Zinc Sulfate; EC Ligase

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