RGD Reference Report - Hypoxia inducible factor-2 a is translationally repressed in response to dietary iron deficiency in Sprague-Dawley rats.

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Hypoxia inducible factor-2 a is translationally repressed in response to dietary iron deficiency in Sprague-Dawley rats.
Authors:	Davis, McKale R Shawron, Krista M Rendina, Elizabeth Peterson, Sandra K Lucas, Edralin A Smith, Brenda J Clarke, Stephen L
Citation:	Davis MR, etal., J Nutr. 2011 Sep;141(9):1590-6. doi: 10.3945/jn.111.144105. Epub 2011 Jul 13.
RGD ID:	12904028
Pubmed:	PMID:21753061 (View Abstract at PubMed)
PMCID:	PMC3735917 (View Article at PubMed Central)
DOI:	DOI:10.3945/jn.111.144105 (Journal Full-text)
Iron regulatory proteins (IRP) regulate cellular iron metabolism by binding to iron-responsive elements (IRE) located in untranslated regions of mRNA-encoding proteins of iron metabolism. Recently, IRE have been identified in mRNA-encoding proteins with previously uncharacterized roles in iron metabolism, thus expanding the role of IRP beyond the regulation of cellular iron homeostasis. The mRNA for HIF 2-α contains an IRE and undergoes iron-dependent regulation in vitro, though the translational regulation of HIF-2α in vivo remains unknown. To examine HIF-2α translational regulation in vivo, we evaluated the effects of iron deficiency on the regulation of hepatic IRP activity and HIF-2α translation. Rats were fed either a control (C; 50 mg Fe/kg diet) or iron-deficient (ID; <5 mg Fe/kg diet) diet or were pair-fed (PF) the C diet for 21 d. In ID rats, there was a 2-fold increase in IRP activity compared to the PF group (P < 0.05), which was reflected by a 30-40% increase in HIF-2α repression (P < 0.05). In agreement with a decrease in translation, the levels of HIF-2α proteins were also decreased. The relative abundance of HIF-2α mRNA did not differ between treatment groups. Taken together, these results suggest that the translation of HIF-2α in the liver is regulated in part by the action of IRP in response to dietary iron deficiency and provide evidence that IRP may assist in coordinating the cellular response to alterations in iron and oxygen status associated with iron deficiency anemia.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ireb2	Rat	response to iron(III) ion		IDA			RGD

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ireb2	Rat	RNA binding		IDA			RGD

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Genes (Rattus norvegicus)

Ireb2 (iron responsive element binding protein 2)

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Hypoxia inducible factor-2 a is translationally repressed in response to dietary iron deficiency in Sprague-Dawley rats.