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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was aimed at determining whether hepcidin, a recently identified peptide involved in iron metabolism, plays a role in conditions associated with both iron overload and iron deficiency. Hepcidin mRNA levels were assessed in two models of anemia, acute hemolysis provoked by phenylhydrazine and bleeding provoked by repeated phlebotomies. Hepcidin response to hypoxia was also studied, both ex vivo, in human hepatoma cells, and in vivo. Anemia and hypoxia were associated with a dramatic decrease in liver hepcidin gene expression, which may account for the increase in iron release from reticuloendothelial cells and increase in iron absorption frequently observed in these situations. A single injection of turpentine for 16 hours induced a sixfold increase in liver hepcidin mRNA levels and a twofold decrease in serum iron. The hyposideremic effect of turpentine was completely blunted in hepcidin-deficient mice, revealing hepcidin participation in anemia of inflammatory states. These modifications of hepcidin gene expression further suggest a key role for hepcidin in iron homeostasis under various pathophysiological conditions, which may support the pharmaceutical use of hepcidin agonists and antagonists in various iron homeostasis disorders.
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PMID:The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. 1237 Feb 82

Juvenile or type 2 hemochromatosis (JH) is a genetic disease caused by increased intestinal iron absorption that leads to early massive iron overload. The main form of the disease is caused by mutations in a still unknown gene on chromosome 1q. Recently, we recognized a second type of JH with clinical features identical to the 1q-linked form, caused by mutations in the gene encoding hepcidin (HEPC). Hepcidin is a hepatic antimicrobial-like peptide whose role in iron homeostasis was first defined in animal models; deficiency of hepcidin in mice leads to iron overload, whereas its hepatic overexpression in transgenic animals causes iron deficiency. To define the prevalence of HEPC mutations in JH we screened the HEPC gene for mutation in 21 unrelated JH subjects. We identified a new mutation (C70R), which affects 1 of the 8 conserved cysteines that form the disulfide bonds and are critical for the stability of the polypeptide.
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PMID:Screening hepcidin for mutations in juvenile hemochromatosis: identification of a new mutation (C70R). 1463 Aug 9

The anaemia of chronic disease (ACD) is a common haematologic syndrome characterized by hypoferraemia with adequate reticuloendothelial iron stores. Frequently, serum ferritin concentration in these patients is elevated. The pathogenesis of ACD involves abnormalities in red cell survival, the erythropoietic response to anaemia, and in iron metabolism. Hepcidin is an antibacterial protein produced in the liver which can be found in blood or urine, and which participates in host defense. Recent studies have demonstrated that hepcidin is a key regulator of iron balance in the intestinal mucosa, and that abnormalities in hepcidin gene expression are associated with clinical abnormalities in iron parameters and, in some cases, with anaemia. Hepcidin is an acute-phase reacting protein, and it has been suggested that hepcidin is the key mediator of ACD. Investigation of hepcidin production in either serum or urine demonstrates a strong correlation with serum ferritin concentration. Differences between the hepcidin concentrations observed in ACD (or syndromes resembling ACD) and those observed in iron deficiency may depend on the definition used for the anaemia syndrome. It seems very likely that hepcidin is a major contributor to iron abnormalities characteristic of ACD; whether it contributes to the pathogenesis of the syndrome in a broader sense remains to be determined by further investigation.
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PMID:Hepcidin and anaemia. 1550 50

Hepcidin is a small cystein-rich cationic peptide produced mainly by the liver. It was initially isolated from human plasma and exhibited antimicrobial activity. Recently, several lines of evidence have suggested that hepcidin is a key regulator of iron metabolism at the whole body level and is relative to inflammation, infection, hypoxia and anemia. Hepcidin, is implicated in duodenal iron absorption and iron mobilization from reticuloendothelial macrophages. The major mechanism of hepcidin function seems to be the regulation of transmembrane iron transport. As both iron deficiency and iron excess are associated with cellular dysfunction, so hepcidin or hepcidin-related therapeutics could find a place in the treatment of various diseases such as hemochromatosis and anemia of chronic disease. To elucidate biological function of hepcidin further and use it for other research, it is necessary to produce enough hepcidin through DNA recombinant technique. As a highly successful system for the production of a variety of heterologous proteins, the methylotrophic Pichia pastoris system has the probability for a high level production of hepcidin. The subject of this paper is to summarize the regulation of hepcidin gene expression and the understanding of functions of hepcidin. At last, giving a prospect of production hepcidin by gene engineer.
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PMID:[Properties and advance of hepcidin]. 1675 11

Both cellular iron deficiency and excess have adverse consequences. To maintain iron homeostasis, complex mechanisms have evolved to regulate cellular and extracellular iron concentrations. Extracellular iron concentrations are controlled by a peptide hormone hepcidin, which inhibits the supply of iron into plasma. Hepcidin acts by binding to and inducing the degradation of the cellular iron exporter, ferroportin, found in sites of major iron flows: duodenal enterocytes involved in iron absorption, macrophages that recycle iron from senescent erythrocytes, and hepatocytes that store iron. Hepcidin synthesis is in turn controlled by iron concentrations, hypoxia, anemia and inflammatory cytokines. The molecular mechanisms that regulate hepcidin production are only beginning to be understood, but its dysregulation is involved in the pathogenesis of a spectrum of iron disorders. Deficiency of hepcidin is the unifying cause of hereditary hemochromatoses, and excessive cytokine-stimulated hepcidin production causes hypoferremia and contributes to anemia of inflammation.
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PMID:Regulation of iron acquisition and iron distribution in mammals. 1679 Feb 83

Iron homeostasis is maintained through meticulous regulation of circulating hepcidin levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. Although hypoxia, erythroid demand, iron, and inflammation are all known to influence hepcidin expression, the mechanisms responsible are not well defined. In this report we show that the inflammatory cytokine interleukin-6 (IL-6) directly regulates hepcidin through induction and subsequent promoter binding of signal transducer and activator of transcription 3 (STAT3). STAT3 is necessary and sufficient for the IL-6 responsiveness of the hepcidin promoter. Our findings provide a mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation.
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PMID:Interleukin-6 induces hepcidin expression through STAT3. 1683 72

Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Hepcidin could also act as an indicator of functional iron deficiency in these patients. Cross-sectional study was performed to assess hepcidin correlations with renal function, iron status, and hsCRP in patients with chronic renal failure on conservative treatment, on hemodialyses, and in kidney transplant recipients. Iron status, complete blood count, creatinine, albumin, lipids were assessed using standard laboratory methods. GFR was estimated using MDRD formula. Hepcidin and high sensitivity CRP were measured using commercially available kits. Ferritin and hepcidin were higher in hemodialyzed patients, kidney transplant recipients, and patients with chronic renal failure over controls. In patients with chronic renal failure, hepcidin correlated significantly with total protein, albumin, creatinine, and eGRF. In kidney transplant recipients, hepcidin correlated significantly in univariate analysis, with total protein, ferritin, time after transplantation, creatinine, eGRF and tended to correlate with cholesterol. In hemodialyzed patients hepcidin, correlated significantly with triglycerides, albumin, creatinine, urea, residual renal function, and hsCRP. In healthy volunteers, hepcidin was related to triglycerides and ferritin. Multiple regression analysis in hemodialyzed patients showed that hepcidin was independently related to creatinine, triglycerides, and residual renal function. Multiple regression analysis in kidney transplant recipients showed that hepcidin was independently related only to GFR and ferritin. Elevated hepcidin in all groups of patients studied may be due to low grade inflammation, frequently encountered in this population and mainly to impaired renal function.
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PMID:Hepcidin, iron status, and renal function in chronic renal failure, kidney transplantation, and hemodialysis. 1692 40

Iron serves as an essential trace element for all body tissues, including the central nervous system (CNS). Because iron deficiency as well as iron overload is known to cause damage to the mammalian brain, the maintenance of iron homeostasis is crucial. It has been discovered recently that hepcidin plays an essential role in iron metabolism outside the CNS. A defect in hepcidin expression is responsible for iron accumulation and mice over-expressing hepcidin die postnatally by a severe anemia. We have used RT-PCR, in situ hybridization, and immunohistochemistry to investigate the cellular distribution of hepcidin mRNA and protein in brain, spinal cord, and dorsal root ganglia. Our results show a wide-spread distribution of hepcidin in different brain areas, including the olfactory bulb, cortex, hippocampus, amygdala, thalamus, hypothalamus, mesencephalon, cerebellum, pons, spinal cord, as well as in dorsal root ganglia of the peripheral nervous system. Hepcidin immunoreactivity is not restricted to neurons, but can be detected in both neurons and GFAP-positive glia cells. Because hepcidin action in organs outside the CNS is linked to iron homeostasis, we speculate that it is also involved in such processes in the CNS, putatively together with other iron regulating proteins. Cellular mechanisms and functions of hepcidin in the CNS remain to be elucidated.
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PMID:Distribution of the iron-regulating protein hepcidin in the murine central nervous system. 1693 19

The knowledge about mammalian iron metabolism has advanced dramatically over the past decades. Studies of genetics, biochemistry and molecular biology allowed us the identification and characterization of many of the molecules involved in regulation of iron homeostasis. Important progresses were made after the discovery in 2000 of a small peptide--hepcidin--that has been proved to play a central role in orchestration on iron metabolism also providing a link between iron metabolism and inflammation and innate immunity. Hepcidin directly interacts with ferroportin (FPN), the only known mammalian iron exporter, which is expressed by enterocytes, macrophages and hepatocytes. The direct hepcidin-FPN interaction allows an adaptative response from the body in situations that alter normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and inflammation).
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PMID:Hepcidin--central regulator of iron metabolism. 1704 75

Heme-regulated eIF2alpha kinase (HRI) plays an essential protective role in anemias of iron deficiency, erythroid protoporphyria, and beta-thalassemia. In this study, we report that HRI protein is present in murine macrophages, albeit at a lower level than in erythroid precursors. Hri-/- mice exhibited impaired macrophage maturation and a weaker antiinflammatory response with reduced cytokine production upon LPS challenge. The level of production of hepcidin, an important player in the pathogenesis of the anemia of inflammation, was significantly decreased in Hri-/- mice, accompanied by decreased splenic macrophage iron content and increased serum iron content. Hepcidin expression was also significantly lower, with a concomitant increase in serum iron in Hri-/- mice upon LPS treatment. We also demonstrated an impairment of erythrophagocytosis by Hri-/- macrophages both in vitro and in vivo under chronic hemolytic anemia, providing evidence for the role of HRI in recycling iron from senescent red blood cells. This work demonstrates that HRI deficiency attenuates hepcidin expression and iron homeostasis in mice, indicating a potential role for HRI in the anemia of inflammation.
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PMID:The function of heme-regulated eIF2alpha kinase in murine iron homeostasis and macrophage maturation. 1793 63


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