Mice are poor heme absorbers and do not require intestinal Hmox1 for dietary heme iron assimilation

Fillebeen, Carine; Gkouvatsos, Konstantinos; Fragoso, Gabriela; Calvé, Annie; Garcia-Santos, Daniel; Buffler, Marzell; Becker, Christiane; Schümann, Klaus; Ponka, Prem; Santos, Manuela M.; Pantopoulos, Kostas

doi:10.3324/haematol.2015.126870

Cited by 40 publications

(29 citation statements)

References 15 publications

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“…Heme oxygenase 1 (Hmox1) is involved in the release of iron from heme29. There are studies shown that rats cannot absorb heme iron as efficiently as humans do, and they don’t require intestinal Hmox1 for dietary heme iron assimilation3031. But glycine was one of the important substrate in the process of heme synthesis32, the increased Hmox1 expression of Fe-Gly group in our experiment indicated that Fe-Gly was more closely linked to intracellular heme metabolism than FeSO 4 .…”

Section: Discussionmentioning

confidence: 99%

Digital gene expression profiling analysis of duodenum transcriptomes in SD rats administered ferrous sulfate or ferrous glycine chelate by gavage

Zhao

Fang

et al. 2016

Sci Rep

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The absorption of different iron sources is a trending research topic. Many studies have revealed that organic iron exhibits better bioavailability than inorganic iron, but the concrete underlying mechanism is still unclear. In the present study, we examined the differences in bioavailability of ferrous sulfate and ferrous glycinate in the intestines of SD rats using Illumina sequencing technology. Digital gene expression analysis resulted in the generation of almost 128 million clean reads, with expression data for 17,089 unigenes. A total of 123 differentially expressed genes with a |log2(fold change)| >1 and q-value < 0.05 were identified between the FeSO4 and Fe-Gly groups. Gene Ontology functional analysis revealed that these genes were involved in oxidoreductase activity, iron ion binding, and heme binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed relevant important pathways. In addition, the expression patterns of 9 randomly selected genes were further validated by qRT-PCR, which confirmed the digital gene expression results. Our study showed that the two iron sources might share the same absorption mechanism, and that differences in bioavailability between FeSO4 and Fe-Gly were not only in the absorption process but also during the transport and utilization process.

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Section: Discussionmentioning

confidence: 99%

Digital gene expression profiling analysis of duodenum transcriptomes in SD rats administered ferrous sulfate or ferrous glycine chelate by gavage

Zhao

Fang

et al. 2016

Sci Rep

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“…HO-1 is probably the main enzyme involved in catabolizing newly absorbed heme (167, 303), but definitive studies are currently lacking. In mice, lack of intestinal HO-1 did not impair heme absorption, although, as recognized by these authors, mice are not able to utilize heme iron very efficiently (80). Other recent studies suggested that HO-2 is the more likely of the two enzymes to be involved in releasing iron from intracellular heme (196).…”

Section: Intestinal Iron Transport: Detailed Mechanistic Descriptionmentioning

confidence: 94%

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Doguer

Collins

2018

Comprehensive Physiology

121

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Iron and copper have similar physiochemical properties; thus, physiologically relevant interactions seem likely. Indeed, points of intersection between these two essential trace minerals have been recognized for many decades, but mechanistic details have been lacking. Investigations in recent years have revealed that copper may positively influence iron homeostasis, and also that iron may antagonize copper metabolism. For example, when body iron stores are low, copper is apparently redistributed to tissues important for regulating iron balance, including enterocytes of upper small bowel, the liver, and blood. Copper in enterocytes may positively influence iron transport, and hepatic copper may enhance biosynthesis of a circulating ferroxidase, ceruloplasmin, which potentiates iron release from stores. Moreover, many intestinal genes related to iron absorption are transactivated by a hypoxia-inducible transcription factor, hypoxia-inducible factor-2α (HIF2α), during iron deficiency. Interestingly, copper influences the DNA-binding activity of the HIF factors, thus further exemplifying how copper may modulate intestinal iron homeostasis. Copper may also alter the activity of the iron-regulatory hormone hepcidin. Furthermore, copper depletion has been noted in iron-loading disorders, such as hereditary hemochromatosis. Copper depletion may also be caused by high-dose iron supplementation, raising concerns particularly in pregnancy when iron supplementation is widely recommended. This review will cover the basic physiology of intestinal iron and copper absorption as well as the metabolism of these minerals in the liver. Also considered in detail will be current experimental work in this field, with a focus on molecular aspects of intestinal and hepatic iron-copper interplay and how this relates to various disease states. © 2018 American Physiological Society. Compr Physiol 8:1433-1461, 2018.

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“…Mice, however, are not good models to study heme iron absorption because they absorb heme very poorly (17). In the 1970s and 1980s, experiments with pig intestine provided evidence that heme is taken up via receptor-mediated endocytosis (18,19), but little progress has been made since then.…”

Section: Dietary Iron Absorption By the Enterocytementioning

confidence: 99%

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Knutson

2017

Journal of Biological Chemistry

121

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Edited by F. Peter GuengerichCellular iron homeostasis is maintained by iron and heme transport proteins that work in concert with ferrireductases, ferroxidases, and chaperones to direct the movement of iron into, within, and out of cells. Systemic iron homeostasis is regulated by the liver-derived peptide hormone, hepcidin. The interface between cellular and systemic iron homeostasis is readily observed in the highly dynamic iron handling of four main cell types: duodenal enterocytes, erythrocyte precursors, macrophages, and hepatocytes. This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease.

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Mice are poor heme absorbers and do not require intestinal Hmox1 for dietary heme iron assimilation

Cited by 40 publications

References 15 publications

Digital gene expression profiling analysis of duodenum transcriptomes in SD rats administered ferrous sulfate or ferrous glycine chelate by gavage

Digital gene expression profiling analysis of duodenum transcriptomes in SD rats administered ferrous sulfate or ferrous glycine chelate by gavage

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

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