Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.

Robert Staroń,Anna Gajowiak,Małgorzata Lenartowicz,Wojciech Krzeptowski,Rafał R Starzyński,Aleksandra Bednarz,Marek Pieszka,Dorine W Swinkels,Iqbal Hamza,Rachel P L Van Swelm,Ewa Smuda,Tamara Korolonek,Paweł Lipiński

doi:10.1371/journal.pone.0181117

Abstract

Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream.

Highlights

Heme, a ferrous iron protoporphyin IX complex, is employed as a prosthetic group in diverse proteins that participate in important biological processes [1]
Supplementation of the diet of piglets with hemoglobin efficiently prevented the deterioration of their hematological indices and plasma iron levels, and rescued them from the severe anemia observed in non-supplemented animals (Table 1)
Recent mammalian studies have demonstrated several proteins involved in the transport of intact heme molecules at both the cellular and systemic levels [5,6,7,35]

Summary

Introduction

A ferrous iron protoporphyin IX complex, is employed as a prosthetic group in diverse proteins that participate in important biological processes [1]. The delivery of iron for heme/hemoglobin synthesis in erythroblasts is indispensable for maintenance of the body iron balance These processes rely on the recovery of iron from senescent erythrocytes, through the circulation. Heme exported to the bloodstream is scavenged by hemopexin (Hpx), an effective heme-binding protein found in blood plasma, which acts primarily to deliver heme to cells via CD91 receptor-mediated endocytosis [9,10] This system is of particular importance when the concentration of free heme reaches toxic levels in the body [5] or locally in cells with an intensive heme metabolism [11]. We hypothesize that the well-known high bioavailability of heme iron may rely on the presence of two independent pathways mediating the transport of hemederived elemental iron and intact heme from the duodenal enterocytes into the circulation

Results

Discussion

Materials and methods

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