Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process. - Archive ouverte HAL
Article Dans Une Revue Journal of Hepatology Année : 2009

Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process.

Résumé

BACKGROUND/AIMS: The iron-regulatory peptide hepcidin is synthesized in the liver as an 84-aa pre-pro-hormone maturated by proteolysis through a consensus furin cleavage site to generate the bioactive 25-aa peptide secreted in the circulation. This peptide regulates iron export from enterocytes and macrophages by binding the membrane iron exporter, ferroportin, leading to its degradation. Whether pro-hepcidin could be secreted and reflect hepcidin levels remains an open question. However, the activity of the pro-peptide on ferroportin degradation has never been addressed. METHODS: To answer this question, we produced recombinant pro-hepcidin, both the wild-type form and a furin cleavage site mutant, and tested their activity on ferroportin levels in macrophagic J774 cells. Furin activity was also modulated using furin inhibitor or siRNA-mediated furin mRNA knockdown. RESULTS: We found that pro-hepcidin could fully induce ferroportin degradation, but only when processed by furin to generate the mature hepcidin-25 form. Pro-hepcidin activity was abolished in the presence of furin inhibitor and diminished after siRNA-mediated knockdown of furin mRNA. Furthermore, the mutated version of pro-hepcidin was completely inefficient at degrading ferroportin in macrophages. CONCLUSIONS: Our results demonstrate that pro-hepcidin lacks biological activity, unless fully maturated by a furin-dependent process to yield the bioactive 25-aa peptide.

Dates et versions

hal-00366732 , version 1 (09-03-2009)

Identifiants

Citer

Bruno Gagliardo, Nicole Kubat, Audrey Faye, Maryse Jaouen, Béatrice Durel, et al.. Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process.. Journal of Hepatology, 2009, 50 (2), pp.394-401. ⟨10.1016/j.jhep.2008.09.018⟩. ⟨hal-00366732⟩
349 Consultations
0 Téléchargements

Altmetric

Partager

More