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Abstract
In summary, iron is an essential trace element and is important for a good health, the total body iron is 4-4.5g most of them incorporated into hemoglobin. Hepcidin is a peptide hormone with important biological effects on iron metabolism beside other carriers and regulators such as TFR, DMT1 and IRP. It has sequence homology to antimicrobial peptides, although whether this function is conserved in vivo remains to be demonstrated. Hepcidin is derived by cleavage of a pre-propeptide; which is formed of 85 amino acids that will be cleaved to pro-hepcidin which is formed of 60 amino acids, then finally hepcidin will be processed and formed by 25 amino acids. Hepcidin has been implicated as a regulator of body iron stores and mutations have been found in some families with juvenile haemochromatosis. Iron balance is probably sensed by Kupffer cells and signalled to hepatocytes by cytokines such as IL-6 so, it has a role in anemia of inflammation and anaemia of chronic disease. Hepcidin interacts directly with ferroportin 1 to control the release of iron from enterocytes and macrophages. It is excreted by the kidney. This peptide is a fascinating addition to the family of molecules involved in iron metabolism.
Many groups tried to demonstrate the role of hepcidin in iron homeostasis as well as, the role of hepcidin in diseases and all of them agreed that the hepcidin has a role in iron absorption through the intestinal cells as increased hepcidin expression will lead to inhibition of intestinal iron absorption through the basolateral membrane of the enterocytes but its role during iron overload and anemia will need further researches to improve that anemia has the upper hand in determination of hepcidin expression in the liver and its level in the blood.
In conclusion, hepcidin is a putative iron regulatory hormone acting by a negative feedback mechanism in which its high level in the blood will lead to inhibition of iron absorption by the intestine and visa versa, inadequate hepcidin gene expression was found in cases of H.H. and up-regulation of hepcidin was found in cases of anemia of chronic illness, but in cases in which anemia and iron overload were found together (e.g. hemolytic anemia) the anemia has the upper-hand in regulation of hepcidin level so, hepcidin will be down-regulated despite of iron overload. For many years fundamental questions on the
regulation of iron metabolism and trafficking in humans have remained unanswered. The discovery of the hemochromatosis (HFE) gene and the advent of molecular genetics have dramatically changed our concepts of these complex processes. It is easy to predict that when further genetically engineered animals will be available, such as the knockout mice for hepcidin, its study will provide the few missing pieces of the puzzle and help to finally define the molecular pathogenesis of hereditary hemochromatosis and anemia of chronic diseases.
Measuring of hepcidin by PCR technique, in which we estimate its mRNA level, is a sophisticated, complex and coasty technique. Nowadays, we can use the ELISA technique to determine pro-hepcidin level in blood or urine which is a good substitution for the assessment of hepcidin level and it is non-invasive, easy to perform, and thus appropriate for routine work. The success of the pro-hepcidin assay is due to its precision, sensitivity, reproducibility, and exact determination of hepcidin in human serum samples. Application of the present ELISA allows, for the first time, detection and determination of
pro-hepcidin in patients suffering from several disorders of iron metabolism and soon hepcidin agonists and antagonists will be used as a therapy. Future studies of hepcidin action and regulation in vivo and in vitro should fill in some of the tantalizing gaps in our understanding of this increasingly complex field.