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

Autor: Jačić JK; Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia., Nikolić L; Institute for Biological Research 'Siniša Stanković', University of Belgrade, 11000 Belgrade, Serbia., Stanković DM; Vinča Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia., Opačić M; Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia., Dimitrijević M; Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia., Savić D; Institute for Biological Research 'Siniša Stanković', University of Belgrade, 11000 Belgrade, Serbia., Šipka SG; Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia., Spasojević I; Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia. Electronic address: redoxsci@gmail.com., Pristov JB; Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2020 Feb 20; Vol. 148, pp. 123-127. Date of Electronic Publication: 2020 Jan 03.
DOI: 10.1016/j.freeradbiomed.2020.01.001
Abstrakt: 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 Fe 3+ 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 Fe 2+ , and the impact of iron on biological activity of Epi are still not known. Herein we showed that Epi and Fe 2+ build colorless complex which is stable under anaerobic conditions. In the presence of O 2 , Epi promoted the oxidation of Fe 2+ and the formation of Epi-Fe 3+ complex. Cyclic voltammetry showed that mid-point potential of Epi-Fe 2+ complex is very low (-582 mV vs. standard hydrogen electrode), which explains catalyzed oxidation of Fe 2+ . 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 Fe 3+ 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-Fe 2+ 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.
Competing Interests: Declaration of competing interest None.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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