How does hepcidin regulate iron metabolism?
Regulation of body iron homeostasis by hepcidin. Hepcidin is secreted primarily by hepatocytes into the circulation, where it functions to inhibit iron absorption in the proximal small intestine and iron release from RE macrophages by binding to its receptor ferroportin and causing its internalization and degradation.
What happens to hepcidin when serum iron increases?
Hepcidin, produced by the liver, is the master regulator of iron balance. Serum hepcidin is increased by high iron stores, blocks intestinal iron absorption, and impairs storage iron release. Conversely, iron deficiency lowers hepcidin levels and enhances intestinal iron absorption and the release of storage iron.
Does hepcidin store iron?
Hepcidin also appears to block, at least partially, the export of stored iron from hepatocytes as indicated by hepatic iron accumulation in mice carrying hepcidin-overproducing tumors. Hepcidin-ferroportin (Fpn) interaction determines the flow of iron into plasma.
What is the role of hepcidin in iron absorption?
Hepcidin, the master regulator of systemic iron homeostasis, tightly influences erythrocyte production. High hepcidin levels block intestinal iron absorption and macrophage iron recycling, causing iron restricted erythropoiesis and anemia.
What are the effects of hepcidin?
What do macrophages do with iron?
Iron within the cytosol of macrophages is utilized as a cofactor in many different cellular proteins that regulate energy production, hypoxic regulation, detoxification, and host defense and inflammation [31]. These proteins contain iron as part of two main cofactors: Iron-sulfur clusters (ISC) and heme groups.
How is hepcidin regulation?
Plasma hepcidin levels are regulated by different stimuli, including cytokines, plasma iron, anemia, and hypoxia. Dysregulation of hepcidin expression results in iron disorders.
Does hepcidin increase oral iron absorption?
Iron supplements at doses of 60 mg Fe as FeSO4 or higher increase hepcidin for up to 24 hours and are associated with lower iron absorption on the following day. The soluble transferrin receptor/ferritin ratio and hepcidin are equivalent predictors of iron absorption from supplements.
Why does hepcidin increase during inflammation?
Inflammation increases interleukin-6 production. The consequent increase in hepcidin blocks macrophage iron release as well as the intestinal absorption of iron, resulting in hypoferremia.
What is the role of hepcidin in iron metabolism?
Hepcidin is the central regulator of systemic iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders.
What happens when hepcidin is elevated in the blood?
Aberrantly increased hepcidin leads to systemic iron deficiency and/or iron restricted erythropoiesis. Furthermore, insufficiently elevated hepcidin occurs in multiple diseases associated with iron overload.
How does overexpression of hepcidin cause iron overload?
Chronic overexpression of hepcidin causes iron-restricted anemia in mice and humans, typically manifested as microcytic, hypochromic anemia. Conversely, hepcidin deficiency in mice and humans results in iron overload with iron deposition in the liver and other parenchyma, and sparing of the macrophage-rich spleen.
How does hepcidin bind to the receptor ferroportin?
Our recent data indicate that hepcidin binding to its receptor requires the involvement of one of the disulfide bonds. However, considering that removal of individual bonds does not dramatically decrease hepcidin activity in vitro, multiple disulfide bonds must be capable of forming a contact with ferroportin.