Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System

Tomosugi, Naohisa; Kawabata, Hiroshi; Wakatabe, Rumi; Higuchi, M.; Yamaya, Hideki; Umehara, Hisanori; Ishikawa, Isao

doi:10.1182/blood-2005-10-4043

Cited by 264 publications

(273 citation statements)

References 32 publications

(55 reference statements)

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“…7 Also, the ELISA used to measure the serum Hepc concentration was not specific for biologically active Hepc-25. 30,49 No practical assay has been reported for measurement of active Hepc-25, although attempts have been made to develop an assay system by using SELDI-TOF MS. 50 Hjv gene expression could be confirmed in skeletal muscle, heart and liver; 51 however, Hjv gene expression was clearly detectable in kidney and in smaller amounts in extrahepatic organs where it was downregulated. In non-HFE-HH, Hepc gene expression was reduced, 51,52 which suggests that Hjv could be involved in Hepc regulation; however, the mechanism is still unclear.…”

Section: Discussionmentioning

confidence: 87%

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Sheikh

Dudás

Ramadori

2007

Laboratory Investigation

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Section: Discussionmentioning

confidence: 87%

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Sheikh

Dudás

Ramadori

2007

Laboratory Investigation

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“…The intensities of the two peaks corresponding to hepcidin-20 and hepcidin-25 were found to be higher in hemodialysis patients compared with healthy volunteers, and a correlation with serum ferritin was found. The authors also reported that hepcidin-25 levels did not seem to fall after a dialysis session in some of the patients (30).…”

Section: Surface Enhanced Laser Desorption/matrix-assisted Laser Desomentioning

confidence: 98%

“…Hepcidin determination in the serum of hemodialysis patients was carried out using SELDI (Ciphergen Biosystems, Freemont, CA), with a reported detection limit of 53 ng/ml (30). The intensities of the two peaks corresponding to hepcidin-20 and hepcidin-25 were found to be higher in hemodialysis patients compared with healthy volunteers, and a correlation with serum ferritin was found.…”

Section: Surface Enhanced Laser Desorption/matrix-assisted Laser Desomentioning

confidence: 99%

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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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“…Attempts to produce correctly folded synthetic hepcidin have proved difficult because the sequence contains eight cysteine residues that constrain the hepcidin molecule in a hairpin structure (Hunter et al 2002). Hepcidin in urine has also been quantified using mass spectrometry methods (Kemna et al 2005;Liang et al 2006;Tomosugi et al 2006).Prohepcidin, the sixty-amino-acid product of cleavage of the signal peptide from the hepcidin precursor, is expressed at the basolateral membrane domain of hepatocytes and is found in blood (Kulaksiz et al 2004). Serum prohepcidin concentrations are significantly lower in patients with hereditary haemochromatosis compared to healthy control subjects (Kulaksiz et al 2004), increase with declining kidney function (Taes et al 2004), and are correlated with haematocrit in chronic haemodialysis patients (Hsu et al 2006), but it is currently unclear whether * Corresponding author: Susan Fairweather-Tait, fax þ 44 1603 452578, email sue.fairweather-tait@bbsrc.ac.uk Abbreviations: DMT1, divalent metal transporter; sTfR, soluble transferrin receptor; LREC, local research ethics committee.…”

mentioning

confidence: 99%

Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women

et al. 2007

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Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes. Hepcidin plays a major role in iron homeostasis, but full characterisation of its role in healthy humans and patients has been hindered by the absence of analytical methods to quantify circulating levels in the blood. Quantification of mRNA in the liver has been undertaken using reverse transcription and the polymerase chain reaction (Bridle et al. 2003;Gehrke et al. 2003), and polyclonal antibodies to refolded synthetic hepcidin have been produced and used for quantification in urine (Nemeth et al. 2003). Attempts to produce correctly folded synthetic hepcidin have proved difficult because the sequence contains eight cysteine residues that constrain the hepcidin molecule in a hairpin structure (Hunter et al. 2002). Hepcidin in urine has also been quantified using mass spectrometry methods (Kemna et al. 2005;Liang et al. 2006;Tomosugi et al. 2006).Prohepcidin, the sixty-amino-acid product of cleavage of the signal peptide from the hepcidin precursor, is expressed at the basolateral membrane domain of hepatocytes and is found in blood (Kulaksiz et al. 2004). Serum prohepcidin concentrations are significantly lower in patients with hereditary haemochromatosis compared to healthy control subjects (Kulaksiz et al. 2004), increase with declining kidney function (Taes et al. 2004), and are correlated with haematocrit in chronic haemodialysis patients (Hsu et al. 2006), but it is currently unclear whether * Corresponding author: ...

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Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System

Abstract: Hepcidin, a key regulator of iron metabolism, is expressed in the liver, distributed in blood, and excreted in urine. However, to date, no reliable and practical method for measuring the bioactive form of hepcidin in serum has been developed. Here, we used surface-enhanced laser desorp-

Cited by 264 publications

References 32 publications

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

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

Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women

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