Abstract
Resveratrol (3,4',5-trihydroxystilbene) is a phytochemical believed to be partly responsible for the cardioprotective effects of red wine due to its numerous biological activities. Here, we studied biochemical pathways underlying peroxynitrite-mediated apoptosis in endothelial cells and potential mechanisms responsible for resveratrol cytoprotective action. Peroxynitrite triggered endothelial cell apoptosis through caspases-8, -9 and -3 activation implying both mitochondrial and death receptor apoptotic pathways. Resveratrol was able to prevent peroxynitrite-induced caspases-3 and -9 activation, but not caspase-8 activation. Additionally, peroxynitrite increased intracellular levels of Bax without affecting those of Bcl-2, increasing consequently the Bax/Bcl-2 ratio. This ratio decreased when cells where pre-incubated with 10 and 50 muM resveratrol, mainly due to resveratrol ability per se to increase Bcl-2 intracellular levels without affecting Bax intracellular levels. These results propose an additional mechanism whereby resveratrol may exert its cardioprotective effects and suggest a key role for Bcl-2 in the resveratrol anti-apoptotic action, especially in disrupting peroxynitrite-triggered mitochondrial pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Apoptosis / drug effects*
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Apoptosis / physiology
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Apoptosis Regulatory Proteins / drug effects
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Apoptosis Regulatory Proteins / metabolism
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Cardiovascular Diseases / drug therapy
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Cardiovascular Diseases / metabolism
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Cardiovascular Diseases / physiopathology
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Caspases / drug effects
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Caspases / metabolism
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Cattle
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Cells, Cultured
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Cytoprotection / drug effects
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Cytoprotection / physiology
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Mitochondria / drug effects*
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Mitochondria / metabolism
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Oxidative Stress / drug effects
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Oxidative Stress / physiology
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Peroxynitrous Acid / antagonists & inhibitors*
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Peroxynitrous Acid / metabolism
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Peroxynitrous Acid / toxicity
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Proto-Oncogene Proteins c-bcl-2 / drug effects*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Death Domain / drug effects
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Receptors, Death Domain / metabolism
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Resveratrol
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Stilbenes / pharmacology*
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Stilbenes / therapeutic use
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bcl-2-Associated X Protein / drug effects
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bcl-2-Associated X Protein / metabolism
Substances
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Antioxidants
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Apoptosis Regulatory Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Death Domain
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Stilbenes
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bcl-2-Associated X Protein
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Peroxynitrous Acid
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Caspases
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Resveratrol