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

Viviana Montecinos, Paula Guzmán, Valeria Barra, Marcelo Villagrán, Carola Muñoz-Montesino, Kirsty Sotomayor, Elizabeth Escobar, Alejandro Godoy, Lorena Mardones, Paula Sotomayor, Catherine Guzmán, Osmán Vásquez, Victoria Gallardo, Brigitte Van Zundert, María Rosa Bono, Sergio A. Oñate, Marcelo Bustamante, Juan G. Cárcamo, Coralia I. Rivas, Juan Carlos Vera

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15506-15515
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number21
DOIs
Publication statusPublished - 25 May 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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