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K. Leung, J. Tombran-Tink; ZIP2 and ZIP4 Zinc Transporters Regulate Intracellular Zinc Levels in Human RPE. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2916.
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Zinc is an essential micronutrient for normal cell function. Imbalance of Zn2+ content in the retina and retinal pigment epithelium appears to be associated with retinal diseases including age-related macular degeneration. We recently reported the expression of zinc transporters in human RPE cells and their alterations with aging. Here we examine the role of ZIP2 and ZIP4 in controlling intracellular zinc levels in RPE cells.
The expression of ZIP2, ZIP4, and metallothionein (MT) in human RPE cells of different ages (9, 52, 76 yr) was examined by PCR, immunocytochemistry, and western blot analysis. Zn2+ uptake was examined using Zinquin ethyl ester and confocal fluorescence microscopy imaging, and quantified by flow cytometry using FluoZin-3. Gene silencing and over-expression of these transporters were achieved by ZIP2 and ZIP4 siRNA and gene expression vectors, respectively.
Our studies show age-dependent decrease in expression of ZIP2 and ZIP4 in RPE cells. Aging RPE cells has lower intracellular Zn2+ levels compared to cells from younger donors. Extracellular Zn2+ supplement stimulates Zn2+ uptake and increases expression of the MT isoforms, MT-1B and MT-1M, in RPE cells. Zn2+ uptake is suppressed by knock-down of ZIP2 and ZIP4 in 9 yr RPE cells and is increased when these transporters are over-expressed in 76 yr RPE cells.
The influx zinc transporters, ZIP2 and ZIP4, are associated with the regulation of Zn2+ imbalance in RPE cells. Modulation in the expression of these transporters may have consequences to Zn2+ homeostasis in the retina.
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