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Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice

Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optim...

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Autores principales: Matak, Pavle, Zumerle, Sara, Mastrogiannaki, Maria, El Balkhi, Souleiman, Delga, Stephanie, Mathieu, Jacques R. R., Canonne-Hergaux, François, Poupon, Joel, Sharp, Paul A., Vaulont, Sophie, Peyssonnaux, Carole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610650/
https://www.ncbi.nlm.nih.gov/pubmed/23555700
http://dx.doi.org/10.1371/journal.pone.0059538
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author Matak, Pavle
Zumerle, Sara
Mastrogiannaki, Maria
El Balkhi, Souleiman
Delga, Stephanie
Mathieu, Jacques R. R.
Canonne-Hergaux, François
Poupon, Joel
Sharp, Paul A.
Vaulont, Sophie
Peyssonnaux, Carole
author_facet Matak, Pavle
Zumerle, Sara
Mastrogiannaki, Maria
El Balkhi, Souleiman
Delga, Stephanie
Mathieu, Jacques R. R.
Canonne-Hergaux, François
Poupon, Joel
Sharp, Paul A.
Vaulont, Sophie
Peyssonnaux, Carole
author_sort Matak, Pavle
collection PubMed
description Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes. How systemic copper status regulates iron absorption is unknown. Mice were subjected to a nutritional copper deficiency-induced anemia regime from birth and injected with copper sulphate intraperitoneally to correct the anemia. Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia inducible factor 2α (HIF-2α) levels, a regulator of iron absorption. HIF-2α upregulation in copper deficiency appeared to be independent of duodenal iron or copper levels and correlated with the expression of iron transporters (Ferroportin - Fpn, Divalent Metal transporter – Dmt1) and ferric reductase – Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper injection resulted in down regulation of HIF-2α-regulated iron absorption genes in the gut. Our work identifies HIF-2α as an important regulator of iron transport machinery in copper deficiency.
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spelling pubmed-36106502013-04-03 Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice Matak, Pavle Zumerle, Sara Mastrogiannaki, Maria El Balkhi, Souleiman Delga, Stephanie Mathieu, Jacques R. R. Canonne-Hergaux, François Poupon, Joel Sharp, Paul A. Vaulont, Sophie Peyssonnaux, Carole PLoS One Research Article Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes. How systemic copper status regulates iron absorption is unknown. Mice were subjected to a nutritional copper deficiency-induced anemia regime from birth and injected with copper sulphate intraperitoneally to correct the anemia. Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia inducible factor 2α (HIF-2α) levels, a regulator of iron absorption. HIF-2α upregulation in copper deficiency appeared to be independent of duodenal iron or copper levels and correlated with the expression of iron transporters (Ferroportin - Fpn, Divalent Metal transporter – Dmt1) and ferric reductase – Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper injection resulted in down regulation of HIF-2α-regulated iron absorption genes in the gut. Our work identifies HIF-2α as an important regulator of iron transport machinery in copper deficiency. Public Library of Science 2013-03-28 /pmc/articles/PMC3610650/ /pubmed/23555700 http://dx.doi.org/10.1371/journal.pone.0059538 Text en © 2013 Matak et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Matak, Pavle
Zumerle, Sara
Mastrogiannaki, Maria
El Balkhi, Souleiman
Delga, Stephanie
Mathieu, Jacques R. R.
Canonne-Hergaux, François
Poupon, Joel
Sharp, Paul A.
Vaulont, Sophie
Peyssonnaux, Carole
Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice
title Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice
title_full Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice
title_fullStr Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice
title_full_unstemmed Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice
title_short Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice
title_sort copper deficiency leads to anemia, duodenal hypoxia, upregulation of hif-2α and altered expression of iron absorption genes in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610650/
https://www.ncbi.nlm.nih.gov/pubmed/23555700
http://dx.doi.org/10.1371/journal.pone.0059538
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