Vitamin C as antioxidant even in presence of GSH excess

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http://www.jbc.org/cgi/content/full/282/21/15506

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J Biol Chem. 2007 May 25;282(21):15506-15. Epub 2007 Apr 2.

*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*.

Montecinos V et al.

Departamento de Fisiopatología, Facultad de Ciencias Biológicas,

Universidad de Concepción, Casilla 160C, Concepción, Chile.

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.

PMID: 17403685

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