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

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

doi:10.3390/nu13010104

Abstract

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.

Highlights

Iron and copper belong to the group of trace elements required for physiological functions and development of the body
Our results suggest that in anemic piglets, intra-enterocytic regulation of iron absorption is largely based on the interaction between copper and iron metabolism proteins and dominates systemic control of iron influx to the body across the duodenum
In 28-dayold piglets deprived of iron supplementation, a significant decrease in the values of most red blood cells (RBCs) indices such as hemoglobin (HB) concentration, hematocrit (HCT) level, and the mean corpuscular volume (MCV) was observed (Table 1)

Summary

Introduction

Iron and copper belong to the group of trace elements required for physiological functions and development of the body. In biological systems, they exist in two oxidation states, which determine their main role—acting as cofactors of numerous cellular enzymes. Intracellular iron and copper associated with a variety of ligands participate in the generation of powerful oxidants, which directly damage proteins, lipids, and nucleic acids [1]. Metabolisms of both metals must be tightly controlled at the systemic and cellular levels.

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