Known and potential roles of transferrin in iron biology

Abstract

Transferrin is an abundant serum metal-binding protein best known for its role in iron delivery. The human disease congenital atransferrinemia and animal models of this disease highlight the essential role of transferrin in erythropoiesis and iron metabolism. Patients and mice deficient in transferrin exhibit anemia and a paradoxical iron overload attributed to deficiency in hepcidin, a peptide hormone synthesized largely by the liver that inhibits dietary iron absorption and macrophage iron efflux. Studies of inherited human disease and model organisms indicate that transferrin is an essential regulator of hepcidin expression. In this paper, we review current literature on transferrin deficiency and present our recent findings, including potential overlaps between transferrin, iron and manganese in the regulation of hepcidin expression.

Exposure to bis(maltolato)oxovanadium(IV) increases levels of hepcidin mRNA and impairs the homeostasis of iron but not that of manganese

“…It has been suggested that Mn might modulate the expression of hepcidin, and therefore changes in the plasma levels of Mn could attenuate or increase hepcidin content (Bartnikas, 2012). It has also been reported that Mn is a substrate for ferroportin, the transport of which seems to be unidirectional (Yin et al, 2010;Madejczyk and Ballatori, 2012).…”

“…Bartnika recently suggested that manganese (Mn), a metal that is transported by DMT-1, may also modulate the expression of hepcidin, and that changes in the plasma levels of Mn could attenuate or increase those of hepcidin (Bartnikas, 2012). However, this author also observed that physiological plasma levels of Mn are much lower (about 100 times lower) than the concentrations shown to be capable of increasing the expression of hepcidin in vitro.…”

Investigating the role of transferrin in the distribution of iron, manganese, copper, and zinc

“…Given that manganese cofractionates with transferrin in vivo, we predicted that both iron and manganese would cofractionate with transferrin while copper and zinc would not. To isolate transferrin-rich fractions, we employed a protocol that segregates transferrin into a low-salt anion exchange fraction [1]. We analyzed pooled serum samples from wt and hpx mice given that our fractionation protocol behaved more consistently with larger starting volumes and serum volumes from individual mice were inadequate.…”

“…Our understanding of the role of the serum protein transferrin in mammalian iron metabolism is based partly on studies of a condition of inherited transferrin deficiency known as hypotransferrinemia [1]. Human cases of hypotransferrinemia are documented yet exceedingly rare.…”

Recent advances in hemochromatosis: a 2015 update

“…Transferrin (Tf) binds to the TfR1 and is taken up into endosomes, where transferrin is cleaved and the receptor recycled back to the cell surface [20]. Excess iron in tissues is stored in complexes of hemosiderin or ferritin.…”