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Vitamin C Affects the Expression of Hepcidin and Erythropoietin Receptor in HepG2 Cells

Published:January 09, 2012DOI:https://doi.org/10.1053/j.jrn.2011.09.007

      Backgrounds

      Hepcidin modulates the de novo absorption of iron from the duodenum and the recycling of iron released from the reticuloendothelial system. In patients with chronic renal failure, administration of higher doses of erythropoietin (EPO) or vitamin C (Vit C) can correct the functional iron deficiency. While EPO-regulated hepcidin expression within hepatocytes has been recently identified, the relation between vitamin C with hepcidin expression is still uncertain.

      Methods

      Hepcidin-producing HepG2 cells (a human liver carcinoma cell line) were cultured with 50- to 100-μg/mL vitamin C or 0.25- to 1.0-U/mL EPO for 6 hours. Reverse transcription polymerase chain reaction was performed for quantitative measurements of hepcidin, EPO, and EPO receptor (EPOR) expression.

      Results

      EPO and vitamin C inhibited hepcidin expression within HepG2 cells; the EPO effect was dose dependent. EPO downregulated EPOR and vitamin C and upregulated EPOR. However, vitamin C had little effect on the expression of EPO.

      Conclusions

      EPO is capable of downregulating EPOR when it acts early. Vitamin C directly inhibits hepcidin expression within HepG2 cells. Moreover, by enhancing EPOR production, vitamin C may correct the downregulating EPOR from EPO, which has additional effect with EPO in treating anemia.
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      References

        • Frazer D.M.
        • Anderson G.J.
        Intestinal iron absorption and its regulation.
        Am J Physiol Gastrointest Liver Physiol. 2005; 289: 631-635
        • Himmelfarb J.
        Iron regulation.
        J Am Soc Nephrol. 2007; 18: 379-381
        • Graham R.M.
        • Chua A.C.
        • Herbison C.E.
        • et al.
        Liver iron transport.
        World J Gastroenterol. 2007; 13: 4725-4736
        • Malyszko J.
        • Mysliwiec M.
        Hepcidin in anemia and inflammation in chronic kidney disease.
        Kidney Blood Press Res. 2007; 30: 15-30
        • Shike H.
        • Lauth X.
        • Westerman M.E.
        • et al.
        Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge.
        Eur J Biochem. 2002; 269: 2232-2237
        • Ganz T.
        Molecular control of iron transport.
        J Am Soc Nephrol. 2007; 18: 394-400
        • Pinto J.P.
        • Ribeiro S.
        • Pontes H.S.
        • et al.
        Erythropoietin mediates hepcidin expression in hepatocytes through EPO-R signaling and regulation of C/EBPα.
        Blood. 2008; 111: 5727-5733
        • Kijima H.
        • Sawada T.
        • Tomosugi N.
        • et al.
        Expression of hepcidin mRNA is uniformly suppressed in hepatocellular carcinoma.
        BMJ Cancer. 2008; 8: 167-174
        • Yokomizo R.
        • Matsuzaki S.
        • Uehara S.
        • et al.
        Erythropoietin and erythropoietin receptor expression in human endometrium throughout the menstrual cycle.
        Mol Hum Reprod. 2002; 8: 441-446
        • Ashby D.R.
        • Gale D.P.
        • Busbridge M.
        • et al.
        Plasma hepcidin levels are elevated but responsive to erythropoietin.
        Kidney Int. 2009; 75: 976-981
        • Weiss G.
        • Theurl I.
        • Eder S.
        • et al.
        Serum hepcidin concentration in chronic hemodialysis patients: associations and effects of dialysis, iron and erythropoietin.
        Eur J of Clin Invest. 2009; 39: 883-890
        • Macdougall I.C.
        Anaemia of chronic kidney disease.
        Medicine. 2007; 35: 457-460
        • Attallah N.
        • Osman-Malik Y.
        • Frinak S.
        • et al.
        Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia.
        Am J Kidney Dis. 2006; 47: 644-654
        • Tarng D.C.
        Novel aspects of vitamin C in epoetin response.
        J Chin Med Assoc. 2007; 70: 357-360
        • Biesalski H.K.
        Parenteral ascorbic acid in haemodialysis patients.
        Curr Opin Clin Nutr Metabolic Care. 2008; 11: 741-746
        • Tarng D.C.
        • Huang T.P.
        A parallel comparative study of intravenous iron versus intravenous ascorbic acid for erythropoietin-hyporesponsive anemia in hemodialysis patients with iron overload.
        Nephrol Dial Transplant. 1998; 13: 2867-2872
        • Richer A.
        • Kuhlmann M.K.
        • Seibert E.
        • et al.
        Vitamin C deficiency and secondary hyperparathyroidism in chronic hemodialysis patients.
        Nephrol Dial Transplant. 2008; 23: 2058-2063