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Cellular vitamin C accumulation in the presence of copper

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Abstract

Under the cell-free condition, copper is known to oxidize ascorbic acid (the active form of vitamin C) and the event leads to the loss of vitamin C. However, the biological consequence of this interaction was never examined in the presence of cells. We demonstrated in intestinal epithelial cells that dehydroascorbic acid (the oxidized form of ascorbic acid), when generated from ascorbic acid in the presence of copper, can be efficiently transported into the cells and reduced back to ascorbic acid. We also observed in other types of cells the transport and intracellular reduction of dehydroascorbic acid in the presence of copper. In the presence of iron, a metal that also oxidizes ascorbic acid, we observed similar oxidation-related accumulation in intestinal cells. Other metals that do not interact with ascorbic acid had little effect on vitamin C transport. A nonmetal pro-oxidant, hydrogen peroxide, is known to oxidize ascorbic acid and we observed that the oxidation is also accompanied by an increased intracellular accumulation of vitamin C. The efficient coupling between dehydroascorbic acid transport and intracellular reduction could help to preserve the important nutrient when facing oxidative metals in the intestine.

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References

  1. A. Hanaki, Copper-catalyzed oxidation of ascorbic acid, Chem. Pharm. Bull. 17, 1839–1846 (1969).

    PubMed  CAS  Google Scholar 

  2. K. Hayakawa and Y. Hayashi, Detection of a complex intermediate in the oxidation of ascorbic acid by the copper(II) ion, J. Nutr. Sci. Vitaminol. 23, 395–401 (1977).

    PubMed  CAS  Google Scholar 

  3. K. Satoh, Y. Ida, S. Kimura, et al., Chelating effect of human serum protein on metalcatalyzed ascorbate radical generation, Anticancer Res. 17, 4377–4380 (1997).

    PubMed  CAS  Google Scholar 

  4. J. I. Ueda, A. Hanaki, K. Hatano, et al., Autooxidation of ascorbic acid catalyzed by the copper(II) bound to l-histidine oligopeptides, (His)iGly and acetyl-(His)I Gly (I=9, 19, 29). Relationship between catalytic activity and coordination mode, Chem. Pharm. Bull. 48, 908–913 (2000).

    PubMed  CAS  Google Scholar 

  5. E. D. Harris and S. S. Percival, A role of ascorbic acid in copper transport, Am. J. Clin. Nutr. 54, 1193S-1197S (1991).

    PubMed  CAS  Google Scholar 

  6. C. S. Tsao and M. Young, Effect of dietary ascorbic acid on levels of serum mineral nutrients in guinea pigs, Int. J. Vitam. Nutr. Res. 59, 72–76 (1989).

    PubMed  CAS  Google Scholar 

  7. G. J. Van den Berg, S. Yu, A. G. Lemmens, et al., Ascorbic acid feeding of rats reduces copper absorption, causing impaired copper status and depressed biliary copper excretion. Biol. Trace Element Res. 41, 47–58 (1994).

    Article  Google Scholar 

  8. H. Tsukaguchi, T. Tokui, B. Mackenzie, et al., A family of mammalian Na+-dependent l-ascorbic acid transporters, Nature 399, 70–75 (1999).

    Article  PubMed  CAS  Google Scholar 

  9. R. Daruwala, J. Song, W. S. Koh, et al., Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2, FEBS Lett. 460, 480–484 (1999).

    Article  PubMed  CAS  Google Scholar 

  10. Y. Wang, B. Mackenzie, H. Tsukaguchi, et al., Human vitamin C (l-ascorbic acid) transporter SVCT1, Biochem. Biophys. Res. Commun. 267, 488–494 (2000).

    Article  PubMed  CAS  Google Scholar 

  11. H. Wang, B. Dutta, W. Huang, et al., Human Na+-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant, Biochim. Biophys. Acta 1461, 1–9 (1999).

    Article  PubMed  CAS  Google Scholar 

  12. J. C. Vera, C. I. Rivas, J. Fischbarg, et al., Mammalian facilitative hexose transporters mediate the transport of dehydroascrobic acid, Nature 364, 79–82 (1993).

    Article  PubMed  CAS  Google Scholar 

  13. S. C. Rumsey, O. Kwon, G. W. Xu, et al., Glucose transport isoforms GLUT1 and GLUT3 transport dehydroascorbic acid, J. Biol. Chem. 272, 18,982–18,989 (1997).

    Article  CAS  Google Scholar 

  14. J. M. May, Z. Qu, and X. Li, Requirement for GSH in recycling of ascorbic acid in endothelial cells, Biochem. Pharmacol. 62, 873–881 (2001).

    Article  PubMed  CAS  Google Scholar 

  15. C. Malo and J. X. Wilson, Glucose modulates vitamin C transport in adult human small intestinal brush border membrane vesicles, J. Nutr. 130, 63–69 (2000).

    PubMed  CAS  Google Scholar 

  16. L. S. Vann, A rapid micro method for determination of ascorbic acid in urine by ferric reduction, Clin. Chem. 11, 979–985 (1965).

    PubMed  CAS  Google Scholar 

  17. J. H. Roe and C. A. Kuether, The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid, J. Biol. Chem. 147, 399–407 (1943).

    CAS  Google Scholar 

  18. S.-M. Kuo, H. F. Morehouse, and C.-P. Lin, Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells. Cancer Lett. 116, 131–137 (1997).

    Article  PubMed  CAS  Google Scholar 

  19. S.-M. Kuo, A. Stout, J. Wactawski-Wende, et al., Ascorbic acid status in postmenopausal women with hormone replacement therapy, Maturitas 41, 45–50 (2002).

    Article  PubMed  CAS  Google Scholar 

  20. B. Sarkar and T. P. Kruck, Separation of Cu(II)-amino acid complexes and evidence for the existence of histidine-Cu(II)-glutamine and histidine-Cu(II)-serum complexes at physiological pH, Can. J. Biochem. 45, 2046–2049 (1967).

    Article  PubMed  CAS  Google Scholar 

  21. G. L. Waldrop and M. J. Ettinger, Effects of albumin and histidine on kinetics of copper transport by fibroblasts, Am. J. Physiol. 259, G212-G218 (1990).

    PubMed  CAS  Google Scholar 

  22. W. H. Kalus and W. G. Filby, The effect of additives on the free radical formation in aqueous solutions of ascorbic acid, Int. J. Vitam. Nutr. Res. 47, 258–264 (1977).

    PubMed  CAS  Google Scholar 

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Kuo, SM., Tan, D. & Boyer, J.C. Cellular vitamin C accumulation in the presence of copper. Biol Trace Elem Res 100, 125–136 (2004). https://doi.org/10.1385/BTER:100:2:125

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  • DOI: https://doi.org/10.1385/BTER:100:2:125

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