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Summary
Author:Lane DJ, Bae DH, Merlot AM, Sahni S, Richardson DR,Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney (Openi/National Library of Medicine) Source:https://openi.nlm.nih.gov/detailedresult?img=PMC4425144_nutrients-07-02274-g002&query=iron%20deficiency&it=xg&req=4&npos=23 Description:nutrients-07-02274-f002: Model for the IRP1-HIF2α axis in regulating DCYTB and dietary iron absorption. (A) Under conditions of iron deficiency (as well as hypoxia or increased erythropoietic drive), the expression of HIF2α is increased in the duodenal enterocyte. This leads to transcriptional up-regulation of key iron-metabolism proteins, including DCYTB, DMT1 and FPN1. Specifically, the increase in HIF2α leads to an augmentation of DCYTB and DMT1 in the brush border (i.e., apical) membrane of the duodenal enterocyte and an increase in FPN1 levels in the basolateral membrane. HIF2α has been shown to bind to HRE elements in the regulatory regions of the promoters for DCYTB and DMT1. HIF2α is also regulated at the post-transcriptional level (as a consequence of the IRE in its 5′-UTR) and post-translational level (as a consequence of PHD activity). Under conditions of iron deficiency in the duodenum, although the increased IRE-binding activity of the IRP1 would tend to decrease HIF2α translation, the stabilizing effect of low PHD activity on HIF2α protein levels may predominate, leading to a net increase in HIF2α and a consequent up-regulation of DCYTB and DMT1. (B) In contrast, under conditions of high iron in the duodenum, HIF2α is translationally derepressed by IRP1, yet PHD activity is likely to be increased, leading to increased HIF2α hydroxylation and proteasomal degradation. The net effect is a decrease in HIF2α levels, resulting in decreased DCYTB, DMT1 and perhaps FPN1 levels.
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| Date/Time | Thumbnail | Dimensions | User | Comment |
current | 18:29, 26 April 2022 | | 512 × 345 (258 KB) | Ozzie10aaaa | Author:Lane DJ, Bae DH, Merlot AM, Sahni S, Richardson DR,Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney (Openi/National Library of Medicine) Source:https://openi.nlm.nih.gov/detailedresult?img=PMC4425144_nutrients-07-02274-g002&query=iron%20deficiency&it=xg&req=4&npos=23 Description:nutrients-07-02274-f002: Model for the IRP1-HIF2α axis in regulating DCYTB and dietary iron absorption. (A) Under conditions of iron deficiency (as... |
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