Vitamin C affects the expression of hepcidin and erythropoietin receptor in HepG2 cells.
BACKGROUND
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.
Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
Ping-Fang
PF
Chiu
Shun-Yao
SY
Ko
Chia-Chu
CC
Chang
D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D015536:Down-Regulation; D004921:Erythropoietin / Q000494:pharmacology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D001205:Ascorbic Acid