Hepcidin and Disorders of Iron Metabolism

Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Annual review of medicine (Impact Factor: 12.93). 01/2010; 62(1):347-60. DOI: 10.1146/annurev-med-050109-142444
Source: PubMed


The hepatic peptide hormone hepcidin is the principal regulator of iron absorption and its tissue distribution. Pathologically increased hepcidin concentrations cause or contribute to iron-restrictive anemias including anemias associated with inflammation, chronic kidney disease and some cancers. Hepcidin deficiency results in iron overload in hereditary hemochromatosis and ineffective erythropoiesis. The hepcidin-ferroportin axis is the principal regulator of extracellular iron homeostasis in health and disease, and is a promising target for the diagnosis and treatment of iron disorders and anemias.

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    • "The pharmacological controls of hepcidin should improve the treatment of various disorders of iron metabolism , including ACD . Different approaches are in study for treatments to control hepcidin ( Ganz and Nemeth , 2011 ; Fung and Nemeth , 2013 ; Poli et al . , 2014c ) and among them we found that heparins strongly repress liver hepcidin expression in vitro and in vivo ( Poli et al . "
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    ABSTRACT: Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites.
    Preview · Article · Jan 2016 · Frontiers in Pharmacology
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    • "Despite their systemic toxicity in different organs, it was recently found to be able to inhibit the expression of hepcidin in hepatocytes through estrogen-like activity, which will lead to increase of serum iron content and reduction of splenic iron content (Wang et al., 2013). PCB-induced iron homeostasis disturbance results in enforced iron supply to other tissues including tumors, which greatly increases the incidence of various cancers and neurological diseases (Ganz and Nemeth, 2011; Zhang et al., 2014). Cadmium (Cd) as an example of heavy metals could disturb systemic iron homeostasis during erythropoiesis. "
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    ABSTRACT: Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants (POPs) and heavy metals has been shown to disturb a specific biological homeostatic process, the iron metabolism in human body. Disorders of iron metabolism are among the common diseases of humans and encompass a broad spectrum of diseases with different clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases and cancer. Hepcidin-ferroportin (FPN) signaling is one of the key mechanisms responsible for iron supply, utilization, recycling, and storage, and recent studies demonstrated that exposure to environmental pollutants including POPs and heavy metals could lead to disruption of the hepcidin-FPN axis along with disordered systemic iron homeostasis and diseases. This article introduces and highlights the accompanying review article by Drs. Xu and Liu in this journal, which elaborates in detail the adverse effects of environmental pollutants on iron metabolism, and the mechanisms responsible for these toxicological outcomes. It also points out the knowledge gaps still existing in this subject matter. Research that will fill these gaps will improve our understanding of the issue and provide useful information to prevent or treat diseases induced by environmental pollutants. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jun 2015 · Journal of Environmental Sciences
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    • "Increased hepcidin expression causes iron deficiency anemia; in contrast, decreased hepcidin expression leads to body iron overload (Ganz and Nemeth, 2011). Iron overload is recognized as a risk factor for cancers, neurodegenerative diseases and arthropathy (Ganz and Nemeth, 2011; Lehmann et al., 2006; Weinberg, 2006). Meanwhile, iron overload is also considered as a risk for osteopenia and osteoporosis (Haidar et al., 2011; Valenti et al., 2009; Weinberg, 2008). "

    Full-text · Dataset · Feb 2015
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