Hepcidin 25 – Inhibitory hormone of iron metabolism
Hepcidin, also known as LEAP-1 (liver-expressed antimicrobial peptide) or Hepcidin-25 is a hormone of 25 amino acids.
Hepcidin is a cationic, cysteine-rich and tightly folded peptide stabilized by 4 disulfide bonds that plays a major role in innate immunity and iron homeostasis.
Hepcidin inhibits iron transport by binding to the iron export channel ferroportin which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages). Hepcidin breaks down the transporter protein in the lysosome. Inhibiting ferroportin prevents iron exportation and iron is retained in cells.
Hepcidin is regulated by iron through a complex of integral hemochromatosis proteins, like HFE, HJV and transferrin receptor 2.
Hepcidin is also characterized by is antimicrobial activity in several vertebrate species, exerting its antimicrobial effect against both Gram-positive and Gram-negative bacteria as well as yeast, with for example an IC50 value against Saccharomyces cerevisae of 18 µM.
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1- Bratescu LO et al. J Ren Nutr (2010)
Accumulating data suggest potential clinical relevant relationships between hepcidin-25 levels, iron stores, erythropoiesis effectiveness, and epoetin dose. The immunometric methods and mass spectroscopy are currently used to measure hepcidin-25, but no standard exists, and values, although similar in trends, differ in absolute value.
To investigate hepcidin levels and their relationship with peripheral iron indices, inflammation, and anemia therapy in patients on hemodialysis (HD).
A cross-sectional study in 78 patients from a single HD center. Hepcidin-25 was measured with enzyme-linked immunosorbent assay (ELISA), using a commercial kit (Bachem, UK).
Hepcidin-25 levels were similar to those previously reported in studies using the same antibody (median 113 [95% CI; 107-122 ng/mL]) and significant but weak correlations of hepcidin with transferrin (R2=0.06; p<0.04) and ferritin (R2=0.09; p<0.01) were found. A model of multiple regression analysis explained 57% of variation along hepcidin quartiles. Lower hepcidin levels were associated with higher transferrin levels (odds ratio 1.05 [1.01-1.09]), bigger iron doses (odds ratio 1.09 [1.02-1.15]), and an increased darbepoetin resistance index (odds ratio 4.3E+15 [11.15-1.6E+30]). An elevated serum C reactive protein was associated with increased hepcidin levels (odds ratio 0.70 [0.49-0.99]), while a higher ultrafiltration volume (odds ratio 4.30 [1.28-14.51]) and the male sex (odds ratio 0.04 [0.00-0.80]) were related to lower hepcidin levels.
Cohort number and composition. Hepcidin-25 ELISA assay.
A low hepcidin level in hemodialysis patients with high epoetin resistance index could be a useful marker of iron-restricted erythropoiesis, but confirmation by a therapeutical trial is necessary.
2- Troutt JS et al. J Clin Lab Anal (2013)
Hepcidin-25 regulates iron homeostasis by binding the iron transporter ferroportin, causing its degradation. Increased hepcidin-25 causes decreased intestinal iron absorption and release from intracellular stores. Our objective in this study was to measure hepcidin-25 levels in patients with chronic kidney disease (CKD) to determine if they might contribute to the anemia of CKD.
We used a hepcidin-25-specific enzyme-linked immunosorbent assay to measure hepcidin-25 in 103 CKD patients and 100 healthy individuals. We assessed in CKD subjects the correlation of hepcidin-25 with creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, blood urea nitrogen, serum iron, transferrin, and ferritin.
Hepcidin-25 concentrations in CKD patients were significantly increased compared to healthy subjects (60.4 ± 6.1 μg/l vs. 3.0 ± 0.5 μg/l, P < 0.001). Hepcidin-25 concentrations were directly correlated with creatinine (R = 0.28, P = 0.004) and inversely correlated with eGFR (R = -0.32, P = 0.001). Hepcidin-25 levels were also correlated with transferrin (R = -0.28, P = 0.004) and ferritin (R = 0.80, P < 0.001).
The direct correlation of hepcidin-25 with creatinine and its inverse correlation with eGFR suggest that hepcidin-25 levels increase as renal function deteriorates, possibly due to decreased hepcidin-25 renal clearance.