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Iron sensing and signalling.
- Source :
-
Gut [Gut] 2012 Jun; Vol. 61 (6), pp. 933-52. Date of Electronic Publication: 2011 Oct 19. - Publication Year :
- 2012
-
Abstract
- Iron deficiency is a common condition increasingly diagnosed and treated by gastroenterologists. The most common presentation of iron deficiency is anaemia; however, it is a systemic disorder affecting multiple aspects of health in various organs. Iron is an essential element, with iron-containing proteins exerting a variety of vital functions, including oxygen transport, cellular respiration, intermediary metabolism, regulation of transcription and DNA repair. Major pathways of iron utilisation and production of iron-containing proteins include iron sulphur cluster biosynthesis, haem synthesis and storage within ferritin. The main site of iron absorption is the small intestine, but most iron is recycled by the monocyte-macrophage system via phagocytosis of senescent erythrocytes. Hepcidin, the key iron-regulating peptide binds to the iron exporter ferroportin and leads to its degradation, thereby inhibiting intestinal iron absorption and cellular export. Hepcidin levels are regulated on a transcriptional level by various stimuli, including transferrin saturation, erythropoietic activity, hypoxia and inflammation. Iron deficiency evokes adaptive responses resulting in alteration of cellular metabolism, changes in gene expression, activation of signalling pathways, cell cycle regulation, differentiation and cell death. Such responses are mediated by a number of iron-sensitive signalling pathways, including the IRE/IRP system, HIF and haem signalling. This review provides a molecular perspective for the clinician and highlights important biological aspects of iron deficiency.
- Subjects :
- Antimicrobial Cationic Peptides physiology
Bone Morphogenetic Proteins physiology
Erythropoiesis physiology
Heme physiology
Heme Oxygenase-1 physiology
Hemochromatosis metabolism
Hemochromatosis physiopathology
Hepcidins
Homeostasis physiology
Humans
Hypoxia-Inducible Factor 1 physiology
Iron metabolism
Iron physiology
Signal Transduction physiology
Iron Deficiencies
Subjects
Details
- Language :
- English
- ISSN :
- 1468-3288
- Volume :
- 61
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Gut
- Publication Type :
- Academic Journal
- Accession number :
- 22016365
- Full Text :
- https://doi.org/10.1136/gut.2010.214312