Endocytic pathway of exogenous iron-loaded ferritin in intestinal epithelial (Caco-2) cells

Antileo, Elmer; Garri, Carolina; Tapia, Victoria; Muñoz, Juan Pablo; Chiong, Mario; Nualart, Francisco; Lavandero, Sergio; Fernández, Juan; Núñez, Marco T.

doi:10.1152/ajpgi.00472.2012

Cited by 18 publications

(14 citation statements)

References 55 publications

(60 reference statements)

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“…Sonicated NP-FePO 4 (200) had a wide particle distribution (150–500 nm), therefore we hypothesize that the smaller particles may be absorbed using clathrin-mediated endocytosis and the larger particles using macropinocytosis. In recent reports, TEM micrographs of nanoparticle uptake have been observed for iron compounds from 10–100 nm size in Caco-2 cells [26,51,52]. Moreover, in support of our findings, a number of previous studies have shown that nano-sized iron compounds are absorbed using endocytic pathways in Caco-2 cells [22,23,26].…”

Section: Discussionsupporting

confidence: 91%

Mechanisms of Iron Uptake from Ferric Phosphate Nanoparticles in Human Intestinal Caco-2 Cells

et al. 2017

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Food fortification programs to reduce iron deficiency anemia require bioavailable forms of iron that do not cause adverse organoleptic effects. Rodent studies show that nano-sized ferric phosphate (NP-FePO4) is as bioavailable as ferrous sulfate, but there is controversy over the mechanism of absorption. We undertook in vitro studies to examine this using a Caco-2 cell model and simulated gastrointestinal (GI) digestion. Supernatant iron concentrations increased inversely with pH, and iron uptake into Caco-2 cells was 2–3 fold higher when NP-FePO4 was digested at pH 1 compared to pH 2. The size and distribution of NP-FePO4 particles during GI digestion was examined using transmission electron microscopy. The d50 of the particle distribution was 413 nm. Using disc centrifugal sedimentation, a high degree of agglomeration in NP-FePO4 following simulated GI digestion was observed, with only 20% of the particles ≤1000 nm. In Caco-2 cells, divalent metal transporter-1 (DMT1) and endocytosis inhibitors demonstrated that NP-FePO4 was mainly absorbed via DMT1. Small particles may be absorbed by clathrin-mediated endocytosis and micropinocytosis. These findings should be considered when assessing the potential of iron nanoparticles for food fortification.

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Section: Discussionsupporting

confidence: 91%

Mechanisms of Iron Uptake from Ferric Phosphate Nanoparticles in Human Intestinal Caco-2 Cells

et al. 2017

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“…Caco-2 monolayer model has been successfully applied to simulative absorption studies involving proteins, peptides, amino acids, and minerals. , To well establish the Caco-2 cell monolayers with enterocyte morphology to mimic in vitro calcium absorption, TEER values between apical and basolateral side of the monolayers were measured, as illustrated in Figure B. The TEER values increased as the incubation time was prolonged, and exceeded 400 Ω × cm 2 at day 12.…”

Section: Resultsmentioning

confidence: 99%

An Exploration of the Calcium-Binding Mode of Egg White Peptide, Asp-His-Thr-Lys-Glu, and In Vitro Calcium Absorption Studies of Peptide–Calcium Complex

Sun

Jin

et al. 2017

J. Agric. Food Chem.

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The binding mode between the pentapeptide (DHTKE) from egg white hydrolysates and calcium ions was elucidated upon its structural and thermodynamics characteristics. The present study demonstrated that the DHTKE peptide could spontaneously bind calcium with a 1:1 stoichiometry, and that the calcium-binding site corresponded to the carboxyl oxygen, amino nitrogen, and imidazole nitrogen atoms of the DHTKE peptide. Moreover, the effect of the DHTKE-calcium complex on improving the calcium absorption was investigated in vitro using Caco-2 cells. Results showed that the DHTKE-calcium complex could facilitate the calcium influx into the cytosol and further improve calcium absorption across Caco-2 cell monolayers by more than 7 times when compared to calcium-free control. This study facilitates the understanding about the binding mechanism between peptides and calcium ions as well as suggests a potential application of egg white peptides as nutraceuticals to improve calcium absorption.

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“…30 μg/dl difference in serum Fe levels between the FeNTA 2 ‐ and nanoFe 3+ ‐treated WT animals is mainly due to differences in the absorption kinetics of the two materials. Studies have shown that the rate of absorption of Fe from ferritin, which contains an Fe 3+ oxohydroxide core very similar to nanoFe 3+ and is taken up by clathrin‐dependent endocytosis (47‐49), is slower than that of soluble Fe in the rat intestine (50). Moreover, our own observations in human volunteers comparing nanoFe 3+ to FeSO 4 support this difference in kinetics (unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice

et al. 2014

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The ferritin core is composed of fine nanoparticulate Fe3+ oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe3+ polyoxohydroxide (nanoFe3+). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe2+ sulfate (FeSO4), nanoFe3+, or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe3+ was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe3+ are equally bioavailable in WT mice, and at wk 8 the mean ± sem hemoglobin increase was 18 ± 7 g/L in the FeSO4 group and 30 ± 5 g/L in the nanoFe3+ group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe3+ is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement.—Aslam, M. F., Frazer, D. M., Faria, N., Bruggraber, S. F. A., Wilkins, S. J., Mirciov, C., Powell, J. J., Anderson, G. J., Pereira, D. I. A. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

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Endocytic pathway of exogenous iron-loaded ferritin in intestinal epithelial (Caco-2) cells

Cited by 18 publications

References 55 publications

Mechanisms of Iron Uptake from Ferric Phosphate Nanoparticles in Human Intestinal Caco-2 Cells

Mechanisms of Iron Uptake from Ferric Phosphate Nanoparticles in Human Intestinal Caco-2 Cells

An Exploration of the Calcium-Binding Mode of Egg White Peptide, Asp-His-Thr-Lys-Glu, and In Vitro Calcium Absorption Studies of Peptide–Calcium Complex

Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice

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