Resveratrol affords protection against peroxynitrite-mediated endothelial cell death: A role for intracellular glutathione.
Atherosclerosis, the main cause of cardiovascular disease (CD), is a chronic inflammatory condition associated with an overproduction of oxidant species, namely peroxynitrite, which is a powerful oxidant that reacts directly with all biomolecules. Glutathione is an efficient scavenger of peroxynitrite, so, modulation of glutathione synthesis may provide a strategy to selectively protect cells from this oxidant. Here, we investigated the ability of resveratrol, a component of red wine, to prevent peroxynitrite-mediated endothelial cells toxicity and the underlying mechanism. Bovine aortic endothelial cells (BAEC) in primary cultures were treated with authentic peroxynitrite and the cell viability and intracellular glutathione contents were assessed. Our results demonstrate that a long pre-incubation (14 h) of BAEC with resveratrol (1-50 microM) leads to the endothelial cells rescue from injury triggered by authentic peroxynitrite by a mechanism of up-regulation of the intracellular GSH content, for the highest resveratrol concentration tested. Considering the importance of GSH in regulation of cell life, this capacity of resveratrol provides a new mechanism for its cardioprotective effects and may contribute to the development of novel therapeutic strategies.
Brito
Paula M
PM
Laboratório de Bioquímica, Faculdade de Farmácia, Universidade de Coimbra and Centro de Neurociências, Universidade de Coimbra, 3000-295 Coimbra, Portugal.
Mariano
Anabela
A
Almeida
Leonor M
LM
Dinis
Teresa C P
TC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002417:Cattle; D048430:Cell Shape; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D013267:Stilbenes; D030421:Peroxynitrous Acid; D019328:Buthionine Sulfoximine; D005978:Glutathione; D000077185:Resveratrol