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Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

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journal contribution
posted on 2007-10-11, 17:20 authored by Tiago L. Duarte, George D. D. Jones
Vitamin C (ascorbic acid, AA) is an important antioxidant in human plasma. It is clear, however, that AA has other important, non-antioxidant roles in cells. Of particular interest is its involvement in iron metabolism, since AA enhances dietary iron absorption, increases the activity of Fe2+-dependent cellular enzymes, promotes Fenton reactions in vitro and was reported to have deleterious effects in individuals with iron overload. Nevertheless, the ability of AA to modulate iron metabolism and enhance iron-dependent damage in cells, tissues and organisms has not been fully elucidated. Here we investigated the effect of AA on iron-mediated oxidative stress in normal human fibroblasts. Incubation with physiologically relevant concentrations of AA was not harmful but sensitised cells towards H2O2-induced, iron-dependent DNA strand breakage and cell death. We also report that AA increased the levels of intracellular catalytic iron and concomitantly modulated the expression of two well established iron-regulated genes, ferritin and transferrin receptor. In summary, we present evidence of a novel, non-antioxidant role of AA in human cells, where it increases iron availability and enhances ROS-mediated, iron-dependent damage. We suggest that AA may exacerbate the deleterious effects of metals in vivo and promote normal tissue injury in situations associated with elevated ROS production.

History

Citation

Free Radical Biology and Medicine, 2007, 43(8), pp.1165-1175

Version

  • AM (Accepted Manuscript)

Published in

Free Radical Biology and Medicine

Publisher

Elsevier

issn

0891-5849

eissn

1873-4596

Copyright date

2007

Available date

2007-10-11

Publisher version

http://www.sciencedirect.com/science/article/pii/S0891584907004984

Notes

This is the authors' final draft of the paper published as Free Radical Biology and Medicine, 2007, 43(8), pp. 1165-1175. The definitive version is available from www.sciencedirect.com, via DOI 10.1016/j.freeradbiomed.2007.07.017

Language

en

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