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rdf:type |
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lifeskim:mentions |
umls-concept:C0030685,
umls-concept:C0208973,
umls-concept:C0242184,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1156273,
umls-concept:C1283071,
umls-concept:C1415529,
umls-concept:C1517892,
umls-concept:C1704666,
umls-concept:C1749467,
umls-concept:C1963578
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-9
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimicrobial Cationic Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FURIN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Furin,
http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HFE2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hfe2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/hepcidin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
111
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
924-31
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17938254-Amino Acid Substitution,
pubmed-meshheading:17938254-Animals,
pubmed-meshheading:17938254-Antimicrobial Cationic Peptides,
pubmed-meshheading:17938254-Bone Morphogenetic Proteins,
pubmed-meshheading:17938254-Cell Differentiation,
pubmed-meshheading:17938254-Cell Hypoxia,
pubmed-meshheading:17938254-Down-Regulation,
pubmed-meshheading:17938254-Furin,
pubmed-meshheading:17938254-GPI-Linked Proteins,
pubmed-meshheading:17938254-HeLa Cells,
pubmed-meshheading:17938254-Homeostasis,
pubmed-meshheading:17938254-Humans,
pubmed-meshheading:17938254-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:17938254-Iron,
pubmed-meshheading:17938254-Iron Overload,
pubmed-meshheading:17938254-Liver,
pubmed-meshheading:17938254-Membrane Proteins,
pubmed-meshheading:17938254-Mice,
pubmed-meshheading:17938254-Muscle, Skeletal,
pubmed-meshheading:17938254-Muscle Cells,
pubmed-meshheading:17938254-Mutation, Missense,
pubmed-meshheading:17938254-Organ Specificity,
pubmed-meshheading:17938254-Oxygen,
pubmed-meshheading:17938254-Protein Isoforms,
pubmed-meshheading:17938254-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis.
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pubmed:affiliation |
Vita-Salute San Raffaele University-Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele, Milan, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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