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Vitamin C Is an Essential Antioxidant That Enhances Survival of Oxidatively Stressed Human Vascular Endothelial Cells in the Presence of a Vast Molar Excess of Glutathione

Cellular glutathione levels may exceed vitamin C levels by 10-fold, generating the question about the real antioxidant role that low intracellular concentrations of vitamin C can play in the presence of a vast molar excess of glutathione. We characterized the metabolism of vitamin C and its relation...

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Published in:The Journal of biological chemistry 2007-05, Vol.282 (21), p.15506-15515
Main Authors: Montecinos, Viviana, Guzmán, Paula, Barra, Valeria, Villagrán, Marcelo, Muñoz-Montesino, Carola, Sotomayor, Kirsty, Escobar, Elizabeth, Godoy, Alejandro, Mardones, Lorena, Sotomayor, Paula, Guzmán, Catherine, Vásquez, Osmán, Gallardo, Victoria, van Zundert, Brigitte, Bono, María Rosa, Oñate, Sergio A., Bustamante, Marcelo, Cárcamo, Juan G., Rivas, Coralia I., Vera, Juan Carlos
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cited_by cdi_FETCH-LOGICAL-c435t-b3681f1acf24f122f3c7b26583f560c3d87a755dd0d1f7ca63f4849dddfba8d63
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container_issue 21
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container_title The Journal of biological chemistry
container_volume 282
creator Montecinos, Viviana
Guzmán, Paula
Barra, Valeria
Villagrán, Marcelo
Muñoz-Montesino, Carola
Sotomayor, Kirsty
Escobar, Elizabeth
Godoy, Alejandro
Mardones, Lorena
Sotomayor, Paula
Guzmán, Catherine
Vásquez, Osmán
Gallardo, Victoria
van Zundert, Brigitte
Bono, María Rosa
Oñate, Sergio A.
Bustamante, Marcelo
Cárcamo, Juan G.
Rivas, Coralia I.
Vera, Juan Carlos
description Cellular glutathione levels may exceed vitamin C levels by 10-fold, generating the question about the real antioxidant role that low intracellular concentrations of vitamin C can play in the presence of a vast molar excess of glutathione. We characterized the metabolism of vitamin C and its relationship with glutathione in primary cultures of human endothelial cells oxidatively challenged by treatment with hydrogen peroxide or with activated cells undergoing the respiratory burst, and analyzed the manner in which vitamin C interacts with glutathione to increase the antioxidant capacity of cells. Our data indicate that: (i) endothelial cells express transporters for reduced and oxidized vitamin C and accumulate ascorbic acid with participation of glutathione-dependent dehydroascorbic acid reductases, (ii) although increased intracellular levels of vitamin C or glutathione caused augmented resistance to oxidative stress, 10-times more glutathione than vitamin C was required, (iii) full antioxidant protection required the simultaneous presence of intracellular and extracellular vitamin C at concentrations normally found in vivo, and (iv) intracellular vitamin C cooperated in enhancing glutathione recovery after oxidative challenge thus providing cells with enhanced survival potential, while extracellular vitamin C was recycled through a mechanism involving the simultaneous neutralization of oxidant species. Therefore, in endothelial cells under oxidative challenge, vitamin C functions as an essential cellular antioxidant even in the presence of a vast molar excess of glutathione.
doi_str_mv 10.1074/jbc.M608361200
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source ScienceDirect Journals; PubMed Central
subjects Antioxidants - pharmacology
Ascorbic Acid - metabolism
Ascorbic Acid - pharmacology
Cell Survival - drug effects
Dose-Response Relationship, Drug
Endothelial Cells - metabolism
Glutathione - pharmacology
Humans
Hydrogen Peroxide - pharmacology
Oxidants - pharmacology
Oxidation-Reduction - drug effects
Oxidative Stress - drug effects
Oxidoreductases - metabolism
Respiratory Burst - drug effects
title Vitamin C Is an Essential Antioxidant That Enhances Survival of Oxidatively Stressed Human Vascular Endothelial Cells in the Presence of a Vast Molar Excess of Glutathione
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