The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.
Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin.
Open accessAbstract
Hepcidin is encoded as an 84 amino acid prepropeptide containing a typical N-terminal 24 amino acid endoplasmic reticulum targeting signal sequence, and a 35 amino acid proregion (pro) with a consensus furin cleavage site immediately followed by the C-terminal 25 amino acid bioactive iron-regulatory hormone (mature peptide). We performed pulse-chase studies of posttranslational processing of hepcidin in human hepatoma HepG2 cells and in primary human hepatocytes induced with bone morphogenic protein (BMP-9). In some experiments, the cells were treated with the furin protease inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone (CMK) or furin siRNA. In the absence of furin inhibitor, hepcidin was found to be processed in less than 1 h and secreted as a 3 kDa form reactive with anti-mature but not anti-pro antibody. In the presence of furin inhibitors or furin siRNA, a 6 kDa form reactive with both anti-pro and anti-mature antibody was rapidly secreted into the medium. Processing was not affected by inhibitors of the hypoxia inducible factor (HIF) pathway, or by treatment with 30 microM holo- or apo-transferrin. In conclusion, the hepatic prohormone convertase furin mediates the posttranslational processing of hepcidin. The proteolytic cleavage of prohepcidin to hepcidin is not regulated by iron-transferrin or the HIF pathway.
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“Proteolytic processing of the prohormone is carried out by furin in a relatively unregulated manner.98”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [98]
Citations
Cites
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Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
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Self-citationHepcidin, a urinary antimicrobial peptide synthesized in the liver
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Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
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Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS
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Suppression of hepcidin during anemia requires erythropoietic activity
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Self-citationHepcidin in iron overload disorders
Papanikolaou, G., Tzilianos, M., Christakis, J. I., Bogdanos, D., Tsimirika, K., MacFarlane, J., Goldberg, Y. P., Sakellaropoulos, N., Ganz, T., & Nemeth, E. (2005) · Blood · doi:10.1182/blood-2004-12-4844 · Cited by 445
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Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge
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Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System
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Nemeth, E., Preza, G. C., Jung, C.-L., Kaplan, J., Waring, A. J., & Ganz, T. (2006) · Blood · doi:10.1182/blood-2005-05-2049 · Cited by 273 · cited 1×
“Hepcidin structure and function is conserved between fish and mammals: hepcidin gene sequences of bony fish and mammals encode similar prepropeptides, hepcidins from humans and bass have nearly identical structural conformations [7;8], and zebrafish hepcidin is fully active in a mammalian bioassay system [9].”
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Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia
Rivera, S., Liu, L., Nemeth, E., Gabayan, V., Sorensen, O. E., & Ganz, T. (2005) · Blood · doi:10.1182/blood-2004-08-3375 · Cited by 196
Self-citationDétivaud, L., Nemeth, E., Boudjéma, K., Turlin, B., Troadec, M., Leroyer, P., Ropert, M., Jacquelinet, S., Courselaud, B., Ganz, T., et al. (2005) · Blood · doi:10.1182/blood-2004-12-4855 · Cited by 191
Posttranslational processing of defensins in immature human myeloid cells
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Intramolecular inhibition of human defensin HNP-1 by its propiece.
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Activated α 2-Macroglobulin is a Principal Defensin-binding Protein
Panyutich, A. V., & Ganz, T. (1991) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb/5.2.101 · Cited by 104
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Iron absorption by healthy women is not associated with either serum or urinary prohepcidin
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Regulation of hepcidin in HepG2 and RINm5F cells
Fein, E., Merle, U., Ehehalt, R., Herrmann, T. R. W., & Kulaksiz, H. (2007) · Peptides · doi:10.1016/j.peptides.2007.01.016 · Cited by 41
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Serum pro-hepcidin and iron markers during uncomplicated pregnancy
Laskowska–Klita, T., Chełchowska, M., Świątek, E., Ambroszkiewicz, J., & Leibschang, J. (2006) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2006.03.011 · Cited by 12
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1 of the 32 references couldn’t be matched to a known paper.
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Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122
Self-citationForging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623
The Role of Hepcidin in Iron Metabolism
Nemeth, E., & Ganz, T. (2009) · Acta Haematologica · doi:10.1159/000243791 · Cited by 607
Mechanisms of mammalian iron homeostasis
Pantopoulos, K., Porwal, S. K., Tartakoff, A., & Devireddy, L. (2012) · Biochemistry · doi:10.1021/bi300752r · Cited by 598
Silvestri, L., Pagani, A., Nai, A., De Domenico, I., Kaplan, J., & Camaschella, C. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.012 · Cited by 555
Metadata
- Authors
- Valore, E. V., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Ganz, Tomas
- ORCID
- Ganz, Tomas
- Venue
- Blood Cells Molecules and Diseases
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 40
- Issue
- 1
- Pages
- 132-138
- ISSN
- 1079-9796 (ISSN-L)
- PMC
- PMC2211381
- OpenAlex
- W2054421541
- Cited by
- 234
- References
- 32
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 1 · 2022: 5 · 2021: 11 · 2020: 9 · 2019: 15 · 2018: 14 · 2017: 11 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 19 · 2012: 15
- FWCI
- 15.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood Cells Molecules and Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065029)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Physical Sciences › Materials Science › Metals and Alloys › Iron and Steelmaking Processes
- Keywords
- hepcidin, furin, prohormone convertases, post-translational processing, prohepcidin, hepatocytes, BMP9, iron regulation, hypoxia-inducible factor, transferrin, proteolytic cleavage, HepG2 cells
- MeSH terms
- Humans, Peptide Fragments, Protein Processing, Post-Translational, Transferrin, Hepatocytes, Antimicrobial Cationic Peptides, Proprotein Convertases, Furin, Hypoxia-Inducible Factor 1, Hepcidins
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