AI Article Synopsis
- Hepcidin regulates iron levels in mammals by binding to the iron transporter ferroportin, leading to ferroportin's degradation and reducing iron export from cells.
- A synthetic peptide mimicking the hepcidin-binding domain (HBD) on ferroportin demonstrates the same binding characteristics as hepcidin itself.
- Hepcidin's binding properties vary with temperature; mammalian hepcidin dissociates more quickly at colder temperatures, unlike hepcidin from cold-blooded vertebrates, highlighting evolutionary differences and offering a way to measure hepcidin levels across species.
Article Abstract
Mammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to ferroportin resulting in degradation of ferroportin and decreased cellular iron export. We identify the hepcidin-binding domain (HBD) on ferroportin and show that a synthetic 19 amino acid peptide corresponding to the HBD recapitulates the characteristics and specificity of hepcidin binding to cell-surface ferroportin. The binding of mammalian hepcidin to ferroportin or the HBD shows an unusual temperature dependency with an increased rate of dissociation at temperatures below 15 degrees C. The increased rate of dissociation is due to temperature- dependent changes in hepcidin structure. In contrast, hepcidin from poikilothermic vertebrates, such as fish or frogs, binds the HBD in a temperature-independent fashion. The affinity of hepcidin for the HBD permits a rapid, sensitive assay of hepcidin from all species and yields insights into the evolution of hepcidin.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660598 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2008.07.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
How I Treat Anemia in Myelofibrosis.
Blood
January 2025
Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, United States.
Anemia is a common consequence of myelofibrosis. The treatment of myelofibrosis-associated anemia is complicated by a multifactorial pathobiology, as well as a lack of therapies that result in normalization of the bone marrow and complete restoration of its function. Established agents that are used to treat anemia in other bone marrow failure states such as myelodysplastic syndromes and aplastic anemia, are used for the treatment of myelofibrosis-associated anemia.
View Article and Find Full Text PDFOur knowledge of which bone marrow cells affect red cell production is still incomplete. To explore the role of osteocytes in the process we performed bulk RNAseq of osteocytes isolated from control and phlebotomized mice. The top-upregulated gene following phlebotomy was , erythroferrone ( ).
View Article and Find Full Text PDFProlonged tamoxifen treatment induces iron deposition and ferroptosis in the liver.
FASEB J
January 2025
Department of Nutrition, Second Military Medical University, Shanghai, China.
Tamoxifen is an inhibitor of estrogen receptors and was originally developed for breast cancer therapy. Besides, tamoxifen is widely used for Cre-estrogen receptor-mediated conditional knockout in transgenic mice. However, we found that the 3-month feeding of 0.
View Article and Find Full Text PDFA Recombinant Antibody Against ALK2 Promotes Tissue Iron Redistribution and Contributes to Anemia Resolution in a Mouse Model of Anemia of Inflammation.
Am J Hematol
January 2025
Keros Therapeutics, Lexington, Massachusetts, USA.
Patients with chronic inflammation are burdened with anemia of inflammation (AI), where inflammatory cytokines inhibit erythropoiesis, impede erythropoietin production, and limit iron availability by inducing the iron regulator hepcidin. High hepcidin hinders iron absorption and recycling, thereby worsening the impaired erythropoiesis by restricting iron availability. AI management is important as anemia impacts quality of life and potentially affects morbidity and mortality.
View Article and Find Full Text PDFImpact of p. Gingivalis-induced chronic apical periodontitis on systemic iron homeostasis via the hepatic IL-6/STAT3/Hepcidin signaling pathway.
Int Immunopharmacol
January 2025
State Key Laboratory of Oral Diseases & National Center of Stomatology & National Clinical Research Center for Oral Diseases & Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:
Background And Aims: Chronic apical periodontitis (CAP), an inflammatory disease of the oral cavity caused by bacterial infections with Porphyromonas gingivalis (P. gingivalis) as a key pathogen, has been associated with systemic effects, potentially influencing distant organs including liver. The liver plays a key role in iron metabolism and immunity by hepcidin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!