Suppressed hepcidin expression correlates with hypotransferrinemia in copper-deficient rat pups but not dams.

Authors: Broderius, M  Mostad, E  Prohaska, JR 
Citation: Broderius M, etal., Genes Nutr. 2012 Jul;7(3):405-14. doi: 10.1007/s12263-012-0293-7. Epub 2012 Mar 29.
Pubmed: (View Article at PubMed) PMID:22457245
DOI: Full-text: DOI:10.1007/s12263-012-0293-7

Copper deficiency leads to anemia but the mechanism is unknown. Copper deficiency also leads to hypoferremia, which may limit erythropoiesis. The hypoferremia may be due to limited function of multicopper oxidases (MCO) hephaestin in enterocytes or GPI-ceruloplasmin in macrophages of liver and spleen whose function as a ferroxidase is thought essential for iron transfer out of cells. Iron release may also be limited by ferroportin (Fpn), the iron efflux transporter. Fpn may be lower following copper deficiency because of impaired ferroxidase activity of MCO. Fpn is also dependent on the liver hormone hepcidin as Fpn is degraded when hepcidin binds to Fpn. Anemia and hypoferremia both down regulate hepcidin by separate mechanisms. Current studies confirmed and extended earlier studies with copper-deficient (CuD) rats that suggested low hepicidin resulted in augmented Fpn. However, current studies in CuD dams failed to confirm a correlation that hepcidin expression was associated with low transferrin receptor 2 (TfR2) levels and also challenged the dogma that holotransferrin can explain the correlation with hepcidin. CuD dams exhibited hypoferremia, low liver TfR2, anemia in some rats, yet no depression in Hamp expression, the hepcidin gene. Normal levels of GDF-15, the putative erythroid cytokine that suppresses hepcidin, were detected in plasma of CuD and iron-deficient (FeD) dams. Importantly, FeD dams did display greatly lower Hamp expression. Normal hepcidin in these CuD dams is puzzling since these rats may need extra iron to meet needs of lactation and the impaired iron transfer noted previously.

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CRRD ID: 11041634
Created: 2016-03-25
Species: All species
Last Modified: 2016-03-25
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.