A role for sex and a common HFE gene variant in brain iron uptake

Kari A. Duck, Elizabeth B. Neely, Ian Simpson, James Connor

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood–brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood–brain barrier.

Original languageEnglish (US)
Pages (from-to)540-548
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2018

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Iron
Brain
Genes
Mutation
Genotype
Proteins
Neurodegenerative Diseases

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

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abstract = "HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood–brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood–brain barrier.",
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A role for sex and a common HFE gene variant in brain iron uptake. / Duck, Kari A.; Neely, Elizabeth B.; Simpson, Ian; Connor, James.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 38, No. 3, 01.03.2018, p. 540-548.

Research output: Contribution to journalArticle

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