| First Author | Matak P | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 3 | Pages | e59538 |
| PubMed ID | 23555700 | Mgi Jnum | J:199885 |
| Mgi Id | MGI:5505733 | Doi | 10.1371/journal.pone.0059538 |
| Citation | Matak P, et al. (2013) Copper deficiency leads to anemia, duodenal hypoxia, upregulation of HIF-2alpha and altered expression of iron absorption genes in mice. PLoS One 8(3):e59538 |
| abstractText | 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 2alpha (HIF-2alpha) levels, a regulator of iron absorption. HIF-2alpha 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-2alpha-regulated iron absorption genes in the gut. Our work identifies HIF-2alpha as an important regulator of iron transport machinery in copper deficiency. |
