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Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors

Authors: Korać Jačić, Jelena; Nikolić, Ljiljana; Stanković, Dalibor; Opačić, Miloš; Dimitrijević, Milena; Savić, Danijela; Grgurić-Šipka, Sanja; +2 Authors

Ferrous iron binding to epinephrine promotes the oxidation of iron and impedes activation of adrenergic receptors

Abstract

Abstract Upon release in response to stress, epinephrine (Epi) may interact with labile iron pool in human plasma with potentially important (patho)physiological consequences. We have shown that Epi and Fe3+ build stable 1:1 high-spin bidentate complex at physiological pH, and that Epi does not undergo degradation in the presence of iron. However, the interactions of Epi with the more soluble Fe2+, and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe2+ build colorless complex which is stable under anaerobic conditions. In the presence of O2, Epi promoted the oxidation of Fe2+ and the formation of Epi-Fe3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe2+ complex is very low (−582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe2+. Next, we examined the impact of iron binding on biological performance of Epi using patch clamping in cell culture with constitutive expression of adrenergic receptors. Epi alone evoked an increase of outward currents, whereas Epi in the complex with Fe3+ did not. This implies that the binding of Epi to adrenergic receptors and their activation is prevented by the formation of complex with iron. Pro-oxidative activity of Epi-Fe2+ complex may represent a link between chronic stress and cardiovascular problems. On the other hand, labile iron could serve as a modulator of biological activity of ligands. Such interactions may be important in human pathologies that are related to iron overload or deficiency.

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Serbia
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Subjects by Vocabulary

Microsoft Academic Graph classification: Standard hydrogen electrode Adrenergic receptor medicine.disease_cause medicine Patch clamp Ligand Chemistry Biological activity Epinephrine Biophysics Ferrous iron binding Oxidative stress medicine.drug

Keywords

Epinephrine, Iron, Ligand, Adrenergic receptor, Biochemistry, Adrenaline, Physiology (medical), Humans, Chelating Agents, Labile iron pool, Receptors, Adrenergic, Reduction potential, Oxidative stress, Oxidation-Reduction

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This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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