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Measurement of Tissue Non-Heme Iron Content using a Bathophenanthroline-Based Colorimetric Assay
Published on: January 31, 2022
Heart Ferroportin Protein Content Is Regulated by Heart Iron Concentration and Systemic Hepcidin Expression
Betty Berezovsky1, Jana Frýdlová1, Iuliia Gurieva1
1Institute of Pathophysiology, First Faculty of Medicine, Charles University, 128 53 Prague, Czech Republic.
Insights
Heart ferroportin protein regulation is primarily controlled by the iron regulatory protein/iron-responsive element system, with the hepcidin-ferroportin axis playing a secondary role in iron homeostasis.
Area of Science:
- Biochemistry
- Physiology
- Molecular Biology
Background:
- Hepcidin is a key regulator of systemic iron metabolism.
- Ferroportin is the sole known cellular iron exporter.
- The interplay between hepcidin and ferroportin is crucial for maintaining iron balance.
Purpose of the Study:
- To investigate the regulation of heart ferroportin protein expression.
- To determine the influence of systemic hepcidin levels on heart ferroportin.
- To explore the role of iron regulatory protein/iron-responsive element system in heart ferroportin regulation.
Main Methods:
- Administration of erythropoietin to C57BL/6J mice to decrease hepcidin.
- Injection of ferric carboxymaltose to increase iron and hepcidin.
- Feeding an iron-deficient diet to Wistar rats.
- Immunoblot analysis of heart ferroportin protein content.
- Measurement of heart non-heme iron content.
Main Results:
- Erythropoietin treatment decreased systemic hepcidin and increased heart ferroportin protein.
- Ferric carboxymaltose increased heart non-heme iron and heart ferroportin protein, overriding hepcidin effects.
- Iron deficiency decreased liver hepcidin, heart non-heme iron, and heart ferroportin protein.
- Heart ferroportin expression is modulated by both hepcidin and intracellular iron levels.
Conclusions:
- Heart ferroportin protein is primarily regulated by the iron regulatory protein/iron-responsive element system.
- The hepcidin-ferroportin axis plays a secondary role in regulating heart ferroportin.
- Intracellular iron availability can override hepcidin-mediated regulation of heart ferroportin.
Abstract:
The purpose of the study was to investigate the expression of ferroportin protein following treatments that affect systemic hepcidin. Administration of erythropoietin to C57BL/6J mice decreased systemic hepcidin expression; it also increased heart ferroportin protein content, determined by immunoblot in the membrane fraction, to approximately 200% of control values. This increase in heart ferroportin protein is very probably caused by a decrease in systemic hepcidin expression, in accordance with the classical regulation of ferroportin by hepcidin. However, the control of heart ferroportin protein by systemic hepcidin could apparently be overridden by changes in heart non-heme iron content since injection of ferric carboxymaltose to mice at 300 mg Fe/kg resulted in an increase in liver hepcidin expression, heart non-heme iron content, and also a threefold increase in heart ferroportin protein content. In a separate experiment, feeding an iron-deficient diet to young Wistar rats dramatically decreased liver hepcidin expression, while heart non-heme iron content and heart ferroportin protein content decreased to 50% of controls. It is, therefore, suggested that heart ferroportin protein is regulated primarily by the iron regulatory protein/iron-responsive element system and that the regulation of heart ferroportin by the hepcidin-ferroportin axis plays a secondary role.
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