Copper deficiency leads to anemia, duodenal hypoxia, upregulation of HIF-2? and altered expression of iron absorption genes in mice.

ABSTRACT: 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 2? (HIF-2?) levels, a regulator of iron absorption. HIF-2? 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-2?-regulated iron absorption genes in the gut. Our work identifies HIF-2? as an important regulator of iron transport machinery in copper deficiency.

SUBMITTER: Matak P 

PROVIDER: S-EPMC3610650 | biostudies-other | 2013

REPOSITORIES: biostudies-other