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Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake

Selenite (HSeO(3)(−)) is a monovalent anion of the essential trace element and micronutrient selenium (Se). In therapeutic concentrations, HSeO(3)(−) has been studied for treating certain cancers, serious inflammatory disorders, and septic shock. Little is known, however, about HSeO(3)(−) uptake int...

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Autores principales: McDermott, Joseph R., Geng, Xiangrong, Jiang, Lan, Gálvez-Peralta, Marina, Chen, Fei, Nebert, Daniel W., Liu, Zijuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085232/
https://www.ncbi.nlm.nih.gov/pubmed/27166256
http://dx.doi.org/10.18632/oncotarget.9205
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author McDermott, Joseph R.
Geng, Xiangrong
Jiang, Lan
Gálvez-Peralta, Marina
Chen, Fei
Nebert, Daniel W.
Liu, Zijuan
author_facet McDermott, Joseph R.
Geng, Xiangrong
Jiang, Lan
Gálvez-Peralta, Marina
Chen, Fei
Nebert, Daniel W.
Liu, Zijuan
author_sort McDermott, Joseph R.
collection PubMed
description Selenite (HSeO(3)(−)) is a monovalent anion of the essential trace element and micronutrient selenium (Se). In therapeutic concentrations, HSeO(3)(−) has been studied for treating certain cancers, serious inflammatory disorders, and septic shock. Little is known, however, about HSeO(3)(−) uptake into mammalian cells; until now, no mammalian HSeO(3)(−) uptake transporter has been identified. The ubiquitous mammalian ZIP8 divalent cation transporter (encoded by the SLC39A8 gene) is bicarbonate-dependent, moving endogenous substrates (Zn(2+), Mn(2+), Fe(2+) or Co(2+)) and nonessential metals such as Cd(2+) into the cell. Herein we studied HSeO(3)(−) uptake in: human and mouse cell cultures, shRNA-knockdown experiments, Xenopus oocytes, wild-type mice and two transgenic mouse lines having genetically altered ZIP8 expression, and mouse erythrocytes ex vivo. In mammalian cell culture, excess Zn(2+) levels and/or ZIP8 over-expression can be associated with diminished viability in selenite-treated cells. Intraperitoneal HSeO(3)(−) causes the largest ZIP8-dependent increases in intracellular Se content in liver, followed by kidney, heart, lung and spleen. In every model system studied, HSeO(3)(−) uptake is tightly associated with ZIP8 protein levels and sufficient Zn(2+) and HCO(3)(−) concentrations, suggesting that the ZIP8-mediated electroneutral complex transported contains three ions: Zn(2+)/(HCO(3)(−))(HSeO(3)(−)). Transporters having three different ions in their transport complex are not without precedent. Although there might be other HSeO(3)(−) influx transporters as yet undiscovered, data herein suggest that mammalian ZIP8 plays a major role in HSeO(3)(−) uptake.
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spelling pubmed-50852322016-10-31 Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake McDermott, Joseph R. Geng, Xiangrong Jiang, Lan Gálvez-Peralta, Marina Chen, Fei Nebert, Daniel W. Liu, Zijuan Oncotarget Research Paper Selenite (HSeO(3)(−)) is a monovalent anion of the essential trace element and micronutrient selenium (Se). In therapeutic concentrations, HSeO(3)(−) has been studied for treating certain cancers, serious inflammatory disorders, and septic shock. Little is known, however, about HSeO(3)(−) uptake into mammalian cells; until now, no mammalian HSeO(3)(−) uptake transporter has been identified. The ubiquitous mammalian ZIP8 divalent cation transporter (encoded by the SLC39A8 gene) is bicarbonate-dependent, moving endogenous substrates (Zn(2+), Mn(2+), Fe(2+) or Co(2+)) and nonessential metals such as Cd(2+) into the cell. Herein we studied HSeO(3)(−) uptake in: human and mouse cell cultures, shRNA-knockdown experiments, Xenopus oocytes, wild-type mice and two transgenic mouse lines having genetically altered ZIP8 expression, and mouse erythrocytes ex vivo. In mammalian cell culture, excess Zn(2+) levels and/or ZIP8 over-expression can be associated with diminished viability in selenite-treated cells. Intraperitoneal HSeO(3)(−) causes the largest ZIP8-dependent increases in intracellular Se content in liver, followed by kidney, heart, lung and spleen. In every model system studied, HSeO(3)(−) uptake is tightly associated with ZIP8 protein levels and sufficient Zn(2+) and HCO(3)(−) concentrations, suggesting that the ZIP8-mediated electroneutral complex transported contains three ions: Zn(2+)/(HCO(3)(−))(HSeO(3)(−)). Transporters having three different ions in their transport complex are not without precedent. Although there might be other HSeO(3)(−) influx transporters as yet undiscovered, data herein suggest that mammalian ZIP8 plays a major role in HSeO(3)(−) uptake. Impact Journals LLC 2016-05-06 /pmc/articles/PMC5085232/ /pubmed/27166256 http://dx.doi.org/10.18632/oncotarget.9205 Text en Copyright: © 2016 McDermott et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
McDermott, Joseph R.
Geng, Xiangrong
Jiang, Lan
Gálvez-Peralta, Marina
Chen, Fei
Nebert, Daniel W.
Liu, Zijuan
Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake
title Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake
title_full Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake
title_fullStr Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake
title_full_unstemmed Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake
title_short Zinc- and bicarbonate-dependent ZIP8 transporter mediates selenite uptake
title_sort zinc- and bicarbonate-dependent zip8 transporter mediates selenite uptake
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085232/
https://www.ncbi.nlm.nih.gov/pubmed/27166256
http://dx.doi.org/10.18632/oncotarget.9205
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