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Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model

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†Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, and ‡Nanobiotechnology & Bioanalysis Group, Department of Chemical Engineering, Universitat Rovira i Virgili, 43007 Tarragona, Spain
§ Vascular Biology Laboratory, IMBECU-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, 5500 Mendoza, Argentina
∥ Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain
*E-mail: [email protected]
*E-mail: [email protected]
Cite this: J. Agric. Food Chem. 2014, 62, 32, 8085–8093
Publication Date (Web):July 22, 2014
https://doi.org/10.1021/jf5014633
Copyright © 2014 American Chemical Society
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Abstract

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Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable, modulates the activity of numerous signaling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules. Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc. We have previously shown that these polyphenols chelate zinc cations and hypothesized that these flavonoids might be also acting as zinc ionophores, transporting zinc cations through the plasma membrane. To prove this hypothesis, herein, we have demonstrated the capacity of QCT and epigallocatechin-gallate to rapidly increase labile zinc in mouse hepatocarcinoma Hepa 1-6 cells as well as, for the first time, in liposomes. In order to confirm that the polyphenols transport zinc cations across the plasma membrane independently of plasma membrane zinc transporters, QCT, epigallocatechin-gallate, or clioquinol (CQ), alone and combined with zinc, were added to unilamellar dipalmitoylphosphocholine/cholesterol liposomes loaded with membrane-impermeant FluoZin-3. Only the combinations of the chelators with zinc triggered a rapid increase of FluoZin-3 fluorescence within the liposomes, thus demonstrating the ionophore action of QCT, epigallocatechin-gallate, and CQ on lipid membrane systems. The ionophore activity of dietary polyphenols may underlay the raising of labile zinc levels triggered in cells by polyphenols and thus many of their biological actions.

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