Iron regulatory and bactericidal properties of human recombinant hepcidin expressed in Pichia pastoris

Koliaraki, Vasiliki; Marinou, Martha; Samiotaki, Martina; Panayotou, George; Pantopoulos, Kostas; Mamalaki, Avgi

doi:10.1016/j.biochi.2008.01.012

Cited by 29 publications

(37 citation statements)

References 28 publications

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“…3A2). Secreted hepcidin of the correct molecular weight, as compared against purified recombinant peptide, 17 was immunoprecipitated successfully with a monoclonal hepcidin-specific antibody (Fig. 3A3).…”

Section: Hamp Overexpression Enhances Hcv Translation and Replicationmentioning

confidence: 99%

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Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

et al. 2016

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Mechanisms that favor Hepatitis C virus (HCV) persistence over clearance are unclear, but involve defective innate immunity. Chronic infection is characterized by hepatic iron overload, hyperferraemia and hyperferittinaemia. Hepcidin modulates iron egress via ferroportin and its storage in ferritin. Chronic HCV patients have decreased hepcidin, while HCV replication is modified by HAMP silencing. We aimed to investigate interactions between HCV and hepcidin, during acute and chronic disease, and putative alterations in cellular iron homeostasis that enhance HCV propagation and promote viral persistence. Thus, we used HCV JFH-1-infected co-cultures of Huh7.5 hepatoma and THP-1 macrophage cells, HCV patients' sera and Huh7 hepcidin-expressing cells transfected with HCV replicons. Hepcidin levels were elevated in acutely infected patients, but correlated with viral load in chronic patients. HAMP expression was up-regulated early in HCV infection in vitro, with corresponding changes in ferritin and FPN. Hepcidin overexpression enhanced both viral translation and replication. In HCV-infected co-cultures, we observed increased hepcidin, reduced hepatoma ferritin and a concurrent rise in macrophaghic ferritin over time. Altered iron levels complemented amplified replication in hepatoma cells and one replication round in macrophages. Iron-loading of macrophages led to enhancement of hepatic HCV replication through reversed ferritin "flow." Viral transmissibility from infected macrophages to na€ ıve hepatoma cells was induced by iron. We propose that HCV control over iron occurs both by intracellular iron sequestration, through hepcidin, and intercellular iron mobilisation via ferritin, as means toward enhanced replication. Persistence could be achieved through HCV-induced changes in macrophagic iron that enhances viral replication in these cells.

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Section: Hamp Overexpression Enhances Hcv Translation and Replicationmentioning

confidence: 99%

“…17 The transfected cells were grown in the presence of medium with 500 mg/ml G418 and individual clones were obtained by limited dilution. An empty vector cell line (V24) was also constructed, using just pCDNA3.1.…”

Section: Cells Lines and Co-culturesmentioning

confidence: 99%

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

et al. 2016

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“…1A). Detection of these bands has previously been described with this Fpn1 antibody (39), as well as with antibodies raised against different Fpn1 peptides (27, 40 -43). These studies suggested the lower molecular weight band corresponds to Fpn1 isoforms/products derived from post-translational modification(s), such as protein cleavage (27, 39 -43).…”

Section: Hepcidin Reduces Fpn1mentioning

confidence: 99%

Hepcidin Bound to α2-Macroglobulin Reduces Ferroportin-1 Expression and Enhances Its Activity at Reducing Serum Iron Levels

Huang

Austin

Sari

et al. 2013

Journal of Biological Chemistry

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Background:Hepcidin is the hormone of iron metabolism that is bound by ␣ 2 -macroglobulin (␣ 2 M) and its activated counterpart (␣ 2 M-MA). Results: Serum iron is reduced to a greater extent in mice treated with ␣ 2 M⅐hepcidin or ␣ 2 M-MA⅐hepcidin relative to unbound hepcidin. Conclusion: ␣ 2 M retards hepcidin excretion by the kidney, increasing its efficacy. Significance: These results are important for understanding hepcidin transport and detection in blood.

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“…Recently, Koliaraki and colleagues reported an ELISA assay for hepcidin using a recombinant peptide GA-Hep-FDH6 (recHep ELISA) (24) and polyclonal antibodies raised against this peptide (25). This ELISA assay has a detection range of 11 to 1395 ng/ml, with a detection limit of 5.6 ng/ml.…”

Section: Elisamentioning

confidence: 99%

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Macdougall¹,

Małyszko²,

Hider³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

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Iron regulatory and bactericidal properties of human recombinant hepcidin expressed in Pichia pastoris

Cited by 29 publications

References 28 publications

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

Hepcidin Bound to α2-Macroglobulin Reduces Ferroportin-1 Expression and Enhances Its Activity at Reducing Serum Iron Levels

Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

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