Iron regulates the uptake of ascorbic acid and the expression of sodium-dependent vitamin C transporter 1 (SVCT1) in human intestinal Caco-2 cells

Ascorbic acid (vitamin C) has major effects on the intestinal uptake and utilisation of Fe in humans. The objective of the present study wasto investigate the impact of Fe on the acquisition of ascorbic acid. The strategy was to study the cellular uptake and transport of ascorbicacid in the presence of Fe and also to observe the expression of the Na-dependent vitamin C transporter 1 (SVCT1) protein in humanintestinal Caco-2 cells. SVCT1 is involved in the cellular uptake of ascorbic acid and is therefore a candidate for playing a role in the regulationof Fe utilisation. Caco-2 cells were cultured on transmembrane inserts in a three-compartment system followed by treatment withvarious combinations of FeCl2.4H2O (10–20mmol/l) and sodium ascorbate (150 mmol/l). ELISA and Western blot analyses revealedthat both SVCT1 and ferritin expressions were up-regulated in the presence of ascorbic acid in the basal compartment underneath thecells (10 and 22 %, respectively). Furthermore, when cells deficient in ascorbic acid were exposed to Fe, SVCT1 expression increasedsignificantly (23\ub77 %). The increase in SVCT1 expression correlated with an increase in ascorbic acid uptake (285 %) in Fe-treated cells,as indicated by the SVCT1 inhibitor quercetin. We conclude that Fe plays an important role in regulating the uptake of ascorbic acid inhuman intestinal Caco-2 cells. This new angle could change the conceptual thinking of Fe and ascorbic acid utilisation and assist in thetreatment and prevention of ascorbic acid-deficiency syndromes such as scurvy