| Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. | |
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MedLine Citation:
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PMID: 17938254 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The liver peptide hepcidin regulates iron absorption and recycling. Hemojuvelin (HJV) has a key role in hepcidin regulation, and its inactivation causes severe iron overload both in humans and in mice. Membrane HJV (m-HJV) acts as a coreceptor for bone morphogenetic proteins (BMPs), whereas soluble HJV (s-HJV) may down-regulate hepcidin in a competitive way interfering with BMP signaling. s-HJV is decreased by iron in vitro and increased by iron deficiency in vivo. However, the mechanisms regulating the 2 HJV isoforms remain unclear. Here we show that s-HJV originates from a furin cleavage at position 332-335. s-HJV is reduced in the cleavage mutant R335Q as well as in cells treated with a furin inhibitor, and increased in cells overexpressing exogenous furin, but not in cells overexpressing an inactive furin variant. Furin is up-regulated by iron deficiency and hypoxia in association with the stabilization of HIF-1alpha. Increased s-HJV in response to HIF-1alpha occurs during differentiation of murine muscle cells expressing endogenous Hjv. Our data are relevant to the mechanisms that relate iron metabolism to the hypoxic response. The release of s-HJV might be a tissue-specific mechanism, signaling the local iron requests of hypoxic skeletal muscles independently of the oxygen status of the liver. |
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Authors:
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Laura Silvestri; Alessia Pagani; Clara Camaschella |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-10-15 |
Journal Detail:
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Title: Blood Volume: 111 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2008-01-09 Completed Date: 2008-03-11 Revised Date: 2012-02-24 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 924-31 Citation Subset: AIM; IM |
Affiliation:
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Vita-Salute San Raffaele University-Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele, Milan, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Animals Antimicrobial Cationic Peptides / biosynthesis, genetics Bone Morphogenetic Proteins / genetics, metabolism Cell Differentiation / physiology Cell Hypoxia / physiology Down-Regulation / physiology Furin / genetics, metabolism* GPI-Linked Proteins HeLa Cells Homeostasis / physiology* Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics, metabolism Iron / deficiency, metabolism* Iron Overload / genetics, microbiology* Liver / cytology, metabolism* Membrane Proteins / genetics, metabolism* Mice Muscle Cells / cytology, metabolism Muscle, Skeletal / cytology, metabolism Mutation, Missense Organ Specificity / physiology Oxygen / metabolism Protein Isoforms / genetics, metabolism Signal Transduction / physiology |
| Grant Support | |
ID/Acronym/Agency:
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GTF05007//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Antimicrobial Cationic Peptides; 0/Bone Morphogenetic Proteins; 0/GPI-Linked Proteins; 0/HFE2 protein, human; 0/HIF1A protein, human; 0/Hfe2 protein, mouse; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Membrane Proteins; 0/Protein Isoforms; 0/hepcidin; 7439-89-6/Iron; 7782-44-7/Oxygen; EC 3.4.21.75/FURIN protein, human; EC 3.4.21.75/Furin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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