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

HUSAM DABBAGH-BAZARBACHI; GAEL CLERGEAUD; ISABEL M. QUESADA; MAYRELI ORTIZ; CIARA K. O'SULLIVAN; JUAN FERNÁNDEZ-LARREA

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2014 vol. 62 p. 8085 - 8093

0021-8561

Labile zinc - a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable - modulates the activity of numerous signalling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin and epigallocatechin-gallate act as antioxidants and as signalling 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 quercetin 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 of zinc cations across the plasma membrane independently of plasma membrane zinc transporters, quercetin, epigallocatechin-gallate or clioquinol, alone and combined with zinc, were added to unilamellar dipalmitoylphosphocholine/cholesterol liposomes loaded with membrane-impermeant FluoZinTM-3. Only the combinations of the chelators with zinc triggered a rapid increase of FluoZinTM-3 fluorescence within liposomes, thus demonstrating, the ionophore action of quercetin, epigallocatechin-gallate and clioquinol 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.