Nutrients (2021-12-01)

Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets

  • Aneta Jończy,
  • Rafał Mazgaj,
  • Rafał Radosław Starzyński,
  • Piotr Poznański,
  • Mateusz Szudzik,
  • Ewa Smuda,
  • Marian Kamyczek,
  • Paweł Lipiński

DOI
https://doi.org/10.3390/nu13010104
Journal volume & issue
Vol. 13, no. 104
p. 104

Abstract

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In mammals, 2 × 1012 red blood cells (RBCs) are produced every day in the bone marrow to ensure a constant supply of iron to maintain effective erythropoiesis. Impaired iron absorption in the duodenum and inefficient iron reutilization from senescent RBCs by macrophages contribute to the development of anemia. Ferroportin (Fpn), the only known cellular iron exporter, as well as hephaestin (Heph) and ceruloplasmin, two copper-dependent ferroxidases involved in the above-mentioned processes, are key elements of the interaction between copper and iron metabolisms. Crosslinks between these metals have been known for many years, but metabolic effects of one on the other have not been elucidated to date. Neonatal iron deficiency anemia in piglets provides an interesting model for studying this interplay. In duodenal enterocytes of young anemic piglets, we identified iron deposits and demonstrated increased expression of ferritin with a concomitant decline in both Fpn and Heph expression. We postulated that the underlying mechanism involves changes in copper distribution within enterocytes as a result of decreased expression of the copper transporter—Atp7b. Obtained results strongly suggest that regulation of iron absorption within enterocytes is based on the interaction between proteins of copper and iron metabolisms and outcompetes systemic regulation.

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