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Nutrients 2018, 10(12), 1874; https://doi.org/10.3390/nu10121874

The Zinc-Metallothionein Redox System Reduces Oxidative Stress in Retinal Pigment Epithelial Cells

1
Instituto Universitario Fernández-Vega (Fundación de Investigación Oftalmológica, Universidad de Oviedo), 33012 Oviedo, Spain
2
Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Julián Clavería, 8, 33006 Oviedo, Spain
3
Instituto Oftalmológico Fernández-Vega, Avda. Dres. Fernández-Vega, 34, 33012 Oviedo, Spain
4
Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, 300 George St, 8100A, New Haven, CT 06510, USA
*
Authors to whom correspondence should be addressed.
Received: 6 November 2018 / Revised: 22 November 2018 / Accepted: 27 November 2018 / Published: 2 December 2018
(This article belongs to the Special Issue Health Effects of Dietary Zinc)
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Abstract

Oxidative stress affects all the structures of the human eye, particularly the retina and its retinal pigment epithelium (RPE). The RPE limits oxidative damage by several protective mechanisms, including the non-enzymatic antioxidant system zinc-metallothionein (Zn-MT). This work aimed to investigate the role of Zn-MT in the protection of RPE from the oxidative damage of reactive oxygen intermediates by analytical and biochemical-based techniques. The Zn-MT system was induced in an in vitro model of RPE cells and determined by elemental mass spectrometry with enriched isotopes and mathematical calculations. Induced-oxidative stress was quantified using fluorescent probes. We observed that 25, 50 or 100 μM of zinc induced Zn-MT synthesis (1.6-, 3.6- and 11.9-fold, respectively), while pre-treated cells with zinc (25, 50, and 100 μM) and subsequent 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH) treatment increased Zn-MT levels in a lesser extent (0.8-, 2.1-, 6.1-fold, respectively), exerting a stoichiometric transition in the Zn-MT complex. Moreover, AAPH treatment decreased MT levels (0.4-fold), while the stoichiometry remained constant or slightly higher when compared to non-treated cells. Convincingly, induction of Zn-MT significantly attenuated oxidative stress produced by free radicals’ generators. We conclude that the stoichiometry of Zn-MT plays an important role in oxidative stress response, related with cellular metal homeostasis. View Full-Text
Keywords: zinc; supplementation; metallothioneins; Zn-MT stoichiometry; retinal pigment epithelial cells; oxidative stress; mass-spectrometry zinc; supplementation; metallothioneins; Zn-MT stoichiometry; retinal pigment epithelial cells; oxidative stress; mass-spectrometry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rodríguez-Menéndez, S.; García, M.; Fernández, B.; Álvarez, L.; Fernández-Vega-Cueto, A.; Coca-Prados, M.; Pereiro, R.; González-Iglesias, H. The Zinc-Metallothionein Redox System Reduces Oxidative Stress in Retinal Pigment Epithelial Cells. Nutrients 2018, 10, 1874.

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