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Hamp1 but not Hamp2 regulates ferroportin in fish with two functionally distinct hepcidin types
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Hamp1 but not Hamp2 regulates ferroportin in fish with two functionally distinct hepcidin types
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Journal Article
Hamp1 but not Hamp2 regulates ferroportin in fish with two functionally distinct hepcidin types
2017
Overview
Hepcidin is a small cysteine rich peptide that regulates the sole known cellular iron exporter, ferroportin, effectively controlling iron metabolism. Contrary to humans, where a single hepcidin exists, many fish have two functionally distinct hepcidin types, despite having a single ferroportin gene. This raises the question of whether ferroportin is similarly regulated by the iron regulator Hamp1 and the antimicrobial Hamp2. In sea bass (
Dicentrarchus labrax
), iron overload prompted a downregulation of ferroportin, associated with an upregulation of
hamp1
, whereas an opposite response was observed during anemia, with no changes in
hamp2
in either situation. During infection, ferroportin expression decreased, indicating iron withholding to avoid microbial proliferation.
In vivo
administration of Hamp1 but not Hamp2 synthetic peptides caused significant reduction in ferroportin expression, indicating that in teleost fish with two hepcidin types, ferroportin activity is mediated through the iron-regulator Hamp1, and not through the dedicated antimicrobial Hamp2. Additionally,
in vitro
treatment of mouse macrophages with fish Hamp1 but not Hamp2 caused a decrease in ferroportin levels. These results raise questions on the evolution of hepcidin and ferroportin functional partnership and open new possibilities for the pharmaceutical use of selected fish Hamp2 hepcidins during infections, with no impact on iron homeostasis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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