TAILIEUCHUNG - Báo cáo khoa học: Production of biologically active forms of recombinant hepcidin, the iron-regulatory hormone

Hepcidin is a liver produced cysteine-rich peptide hormone that acts as the central regulator of body iron metabolism. Hepcidin is synthesized under the form of a precursor, prohepcidin, which is processed to produce the biologically active mature 25 amino acid peptide. | ỊFEBS Journal Production of biologically active forms of recombinant hepcidin the iron-regulatory hormone Bruno Gagliardo1 Audrey Faye2 3 Maryse Jaouen1 Jean-Christophe Deschemin2 3 Francois Canonne-Hergaux4 Sophie Vaulont2 3 and Marie-Agnes Sari1 1 CNRS UMR 8601 Université Paris Descartes France 2 Institut Cochin CNRS UMR 8104 Universite Paris Descartes France 3 Inserm U567 Universite Paris Descartes France 4 CNRS ICSN Gif-Sur-Yvette France Keywords antimicrobialpeptide Escherichia coli expression ferroportin hepcidin iron homeostasis Correspondence . Sari UMR 8601 Universite Paris Descartes 45 rue des Saints-Peres 75006 Paris France Fax 33 1428 68387 Tel 33 1428 62142 E-mail Received 1 April2008 revised 22 May 2008 accepted 28 May 2008 doi Hepcidin is a liver produced cysteine-rich peptide hormone that acts as the central regulator of body iron metabolism. Hepcidin is synthesized under the form of a precursor prohepcidin which is processed to produce the biologically active mature 25 amino acid peptide. This peptide is secreted and acts by controlling the concentration of the membrane iron exporter ferroportin on intestinal enterocytes and macrophages. Hepcidin binds to ferroportin inducing its internalization and degradation thus regulating the export of iron from cells to plasma. The aim of the present study was to develop a novel method to produce human and mouse recombinant hep-cidins and to compare their biological activity towards their natural receptor ferroportin. Hepcidins were expressed in Escherichia coli as thioredoxin fusion proteins. The corresponding peptides purified after cleavage from thioredoxin were properly folded and contained the expected four-disulfide bridges without the need of any renaturation or oxidation steps. Human and mouse hepcidins were found to be biologically active promoting ferro-portin degradation in macrophages. Importantly biologically inactive aggregated

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