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.
abstract: 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.
authors.affiliation: Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160C, Concepción, Chile.
authors.forename: Viviana
authors.initials: V
authors.lastname: Montecinos
authors.forename: Paula
authors.initials: P
authors.lastname: Guzmán
authors.forename: Valeria
authors.initials: V
authors.lastname: Barra
authors.forename: Marcelo
authors.initials: M
authors.lastname: Villagrán
authors.forename: Carola
authors.initials: C
authors.lastname: Muñoz-Montesino
authors.forename: Kirsty
authors.initials: K
authors.lastname: Sotomayor
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Escobar
authors.forename: Alejandro
authors.initials: A
authors.lastname: Godoy
authors.forename: Lorena
authors.initials: L
authors.lastname: Mardones
authors.forename: Paula
authors.initials: P
authors.lastname: Sotomayor
authors.forename: Catherine
authors.initials: C
authors.lastname: Guzmán
authors.forename: Osmán
authors.initials: O
authors.lastname: Vásquez
authors.forename: Victoria
authors.initials: V
authors.lastname: Gallardo
authors.forename: Brigitte
authors.initials: B
authors.lastname: van Zundert
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Bono
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Oñate
authors.forename: Marcelo
authors.initials: M
authors.lastname: Bustamante
authors.forename: Juan G
authors.initials: JG
authors.lastname: Cárcamo
authors.forename: Coralia I
authors.initials: CI
authors.lastname: Rivas
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Vera
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016877:Oxidants; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D005978:Glutathione; D001205:Ascorbic Acid