Iron Transport from Ferrous Bisglycinate and Ferrous Sulfate in DMT1-Knockout Human Intestinal Caco-2 Cells.

Xiaonan Yu,Haoxuan Ding,Jie Feng,Lingjun Chen,Yang Zhao

doi:10.3390/nu11030485

Abstract

This experiment was conducted to investigate the transport characteristics of iron from ferrous bisglycinate (Fe-Gly) in intestinal cells. The divalent metal transporter 1 (DMT1)-knockout Caco-2 cell line was developed by Crispr-Cas9, and then the cells were treated with ferrous sulfate (FeSO4) or Fe-Gly to observe the labile iron pool and determine their iron transport. The results showed that the intracellular labile iron increased significantly with Fe-Gly or FeSO4 treatment, and this phenomenon was evident over a wide range of time and iron concentrations in the wild-type cells, whereas in the knockout cells it increased only after processing with high concentrations of iron for a long time (p < 0.05). DMT1-knockout suppressed the synthesis of ferritin and inhibited the response of iron regulatory protein 1 (IRP-1) and IRP-2 to these two iron sources. The expression of peptide transporter 1 (PepT1) was not altered by knockout or iron treatment. Interestingly, the expression of zinc-regulated transporter (ZRT) and iron-regulated transporter (IRT)-like protein 14 (Zip14) was elevated significantly by knockout and iron treatment in wild-type cells (p < 0.05). These results indicated that iron from Fe-Gly was probably mainly transported into enterocytes via DMT1 like FeSO4; Zip14 may play a certain role in the intestinal iron transport.

Highlights

Iron is one of the essential trace elements and a cofactor for various enzymes
The results showed that there was no significant difference in the expression of any iron transporter in the duodenum of rats administrated with ferrous bisglycinate (Fe-Gly) or FeSO4, suggesting that the amino acid chelated iron may be absorbed by the intestine in the same manner as inorganic iron, which was mainly transported into the intestinal cells via the divalent metal ion transporter divalent metal transporter 1 (DMT1) [19]
To further investigate whether iron from Fe-Gly was transported into enterocytes like inorganic iron via DMT1, we developed a DMT1-knockout Caco-2 cell line by using Crispr-Cas9 and treated the cells with Fe-Gly and FeSO4 to observe the labile iron pool and determine the transport of the two forms of iron

Summary

Introduction

Iron is one of the essential trace elements and a cofactor for various enzymes. It is involved in many important physiological processes, such as oxygen transport, electron transport, tricarboxylic acid cycle, and hemoglobin and myoglobin production. Due to the low bioavailability of inorganic iron, it often causes mineral resources waste and environmental pollution, and its abuse affects human health and animal production [7,8,9]. Recent studies have shown that amino acid chelated iron sources such as Fe-Gly have better iron bioavailability than inorganic iron sources such as FeSO4 [10,11,12,13]. The high bioavailability of amino acid chelated iron may be related to its efficient absorption and transport mechanism

Methods

Results

Discussion

Conclusion