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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3610650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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