High throughput fluorimetric assessment of iron traffic and chelation in iron-overloaded Caenorhabditis elegans
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High throughput fluorimetric assessment of iron traffic and chelation in iron-overloaded Caenorhabditis elegans Breno Pannia Espo´sito Michael Aschner
. Airton Cunha Martins . Rodrigo Rodrigues Victor de Carvalho .
Received: 29 April 2020 / Accepted: 16 September 2020 Ó Springer Nature B.V. 2020
Abstract The nematode Caenorhabditis elegans (C. elegans) is a convenient tool to evaluate iron metabolism as it shares great orthology with human proteins involved in iron transport, in addition to being transparent and readily available. In this work, we describe how wild-type (N2) C. elegans nematodes in the first larval stage can be loaded with acetomethoxycalcein (CAL-AM) and study it as a whole-organism model for both iron speciation and chelator permeability of the labile iron pool (LIP). This model may be relevant for high throughput assessment of molecules intended for chelation therapy of iron overload diseases. Keywords Caenorhabditis elegans Iron Copper Chelator Calcein Fluorescence Desferrioxamine
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10534-020-00250-4) contains supplementary material, which is available to authorized users. B. P. Espo´sito (&) R. R. V. de Carvalho Department of Fundamental Chemistry, Institute of Chemistry, University of Sa˜o Paulo, Sa˜o Paulo, SP, Brazil e-mail: [email protected] A. C. Martins M. Aschner Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
Introduction Iron is the most abundant transition metal in biological systems, where its suitable electron transfer properties and ability to form catalytically active coordination compounds are explored in biochemical processes fundamental for all living organisms. Nevertheless, iron overload is a potentially deleterious condition, precisely due to the high reactivity of the metal, especially under oxygenated environments. In humans, iron overload diseases are the result of either dysregulated iron absorption, or treatments for other conditions (e.g., multiple blood transfusions in thalassemia). A common pharmacological approach for the clinical treatment of iron overload diseases in humans is the administration of iron chelators such as desferrioxamine, deferiprone or deferasirox (Bulbake et al. 2019; Cilibrizzi et al. 2018; Lima et al. 2019; Ma et al. 2012). Pathways of iron metabolism are highly conserved between mammalians and the nematode, Caenorhabditis elegans (C. elegans). In the intestinal epithelial cells of the nematode, the proteins involved in the absorption (SMF-3), storage (FTN-1, FTN-2) and export (FPN 1.1, FPN 1.2, FPN 1.3) of non-heme iron are orthologs of mammalian divalent metal transporter 1 (DMT-1), ferritin and ferroportin, respectively (Wang et al. 2016; Anderson and Leibold 2014). Previous studies have addressed the link between iron dyshomeostasis (increase in the levels of unbound reactive iron), oxidative stress and dopaminergic and
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