Caco-2 cell acquisition of dietary iron(III) invokes a nanoparticulate endocytic pathway

Dora I A Pereira, Bianca I. Mergler, Nuno Faria, Sylvaine F A Bruggraber, Mohamad F. Aslam, Lynsey K. Poots, Laura Prassmayer, Bo Lönnerdal, Andy P. Brown, Jonathan J. Powell

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Dietary non-heme iron contains ferrous [Fe(II)] and ferric [Fe(III)] iron fractions and the latter should hydrolyze, forming Fe(III) oxo-hydroxide particles, on passing from the acidic stomach to less acidic duodenum. Using conditions to mimic the in vivo hydrolytic environment we confirmed the formation of nanodisperse fine ferrihydrite-like particles. Synthetic analogues of these (∼ 10 nm hydrodynamic diameter) were readily adherent to the cell membrane of differentiated Caco-2 cells and internalization was visualized using transmission electron microscopy. Moreover, Caco-2 exposure to these nanoparticles led to ferritin formation (i.e., iron utilization) by the cells, which, unlike for soluble forms of iron, was reduced (p=0.02) by inhibition of clathrin-mediated endocytosis. Simulated lysosomal digestion indicated that the nanoparticles are readily dissolved under mildly acidic conditions with the lysosomal ligand, citrate. This was confirmed in cell culture as monensin inhibited Caco-2 utilization of iron from this source in a dose dependent fashion (p<0.05) whilet soluble iron was again unaffected. Our findings reveal the possibility of an endocytic pathway for acquisition of dietary Fe(III) by the small intestinal epithelium, which would complement the established DMT-1 pathway for soluble Fe(II).

Original languageEnglish (US)
Article numbere81250
JournalPLoS One
Volume8
Issue number11
DOIs
StatePublished - Nov 21 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Pereira, D. I. A., Mergler, B. I., Faria, N., Bruggraber, S. F. A., Aslam, M. F., Poots, L. K., Prassmayer, L., Lönnerdal, B., Brown, A. P., & Powell, J. J. (2013). Caco-2 cell acquisition of dietary iron(III) invokes a nanoparticulate endocytic pathway. PLoS One, 8(11), [e81250]. https://doi.org/10.1371/journal.pone.0081250