Systemic Regulation of Intestinal Iron Absorption

Abstract

SummaryThe intestinal absorption of the essential trace element iron and its mobilization from storage sites in the body are controlled by systemic signals that reflect tissue iron requirements. Recent advances have indicated that the liver-derived peptide hepcidin plays a central role in this process by repressing iron release from intestinal enterocytes, macrophages and other body cells. When iron requirements are increased, hepcidin levels decline and more iron enters the plasma. It has been proposed that the level of circulating diferric transferrin, which reflects tissue iron levels, acts as a signal to alter hepcidin expression. In the liver, the proteins HFE, transferrin receptor 2 and hemojuvelin may be involved in mediating this signal as disruption of each of these molecules decreases hepcidin expression. Patients carrying mutations in these molecules or in hepcidin itself develop systemic iron loading (or hemochromatosis) due to their inability to down regulate iron absorption. Hepcidin is also responsible for the decreased plasma iron or hypoferremia that accompanies inflammation and various chronic diseases as its expression is stimulated by pro-inflammatory cytokines such as interleukin 6. The mechanisms underlying the regulation of hepcidin expression and how it acts on cells to control iron release are key areas of ongoing research. IUBMB Life, 57: 499 -503, 2005

Hemojuvelin: The Hepcidin Story Continues

“…HJV indeed plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway, although through unknown mechanisms [7] . It has been reported that HFE, HJV, TfR2 and HAMP genes are closely related, but the precise underlying mechanism(s) were not revealed [7,22,23] . For many years the signal transduction pathways that regulate systemic iron homeostasis have been unknown.…”

O efeito do consumo crônico de etanol na absorção duodenal de ferro em camundongos

“…Grande quantidade de fatores externos interfere na absorção de ferro, dificultando a compreensão dos mecanismos reguladores da concentração desse metal no organismo (1,3,5,7,8,11,13,14,17,21) . No presente estudo, procurou-se reduzir a influência externa no mecanismo de absorção, através da perfusão de solução salina com ascorbato de ferro II em alça isolada.…”

“…Quando ocorre aumento da necessidade de ferro, a concentração da hepadicina diminui, aumentando a absorção do ferro. A concentração de transferrina atua como regulador da produção de hepadicina (8,21) . A absorção do ferro inorgânico é influenciada por múltiplos fatores.…”

Modulation of iron metabolism in aging and in Alzheimer's disease: relevance of the choroid plexus

“…When the body is iron-replete, macrophages of the liver, spleen, bone marrow, and reticuloendothelial system can also store iron recovered from the phagocytosis of senescent erythrocytes. Inside the macrophage, iron is released from hemoglobin and can either be stored or released back into the circulation (Steele et al, 2005; Camaschella and Pagani, 2011). Depending on the intracellular iron levels, each cell regulates iron uptake mostly by modulating the expression of TFR1, while the efflux of iron through FPN is regulated systemically under the control of the liver-derived peptide hepcidin (HAMP) (Krause et al, 2000).…”