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• W3020229432 abstract "Abstract Zinc ions (Zn 2+ ) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn 2+ concentration ([Zn 2+ ] c ), Zrt/Irt-related proteins (ZIPs) and Zn 2+ transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the [Zn 2+ ] c , respectively, by fluxing Zn 2+ across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of [Zn 2+ ] c and less investigate the [Zn 2+ ] c at physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the [Zn 2+ ] c to different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the [Zn 2+ ] c by zinc oxide-nanoparticles (ZnO-NP) at concentrations below 1 μg/ml, which had little cytotoxicity, in cultured human neuroblastoma SH-SY5Y cells and characterized the importance of Zn 2+ transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the [Zn 2+ ] c transiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels of ZnT 1 (mostly at the plasma membrane) and ZIP 8 (present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of [Zn 2+ ] c , respectively. ZnO-NP treatment reduced the basal levels of reactive oxygen species and Bax/Bcl-2 mRNA ratios; in addition, ZnO-NP decreased the 6-OHDA-induced ROS production, p53 expression, and cell death. Therefore, mild elevations in [Zn 2+ ] c induced by ZnO-NP activate beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurological disease." @default.
• W3020229432 created "2020-05-01" @default.
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• W3020229432 date "2020-04-22" @default.
• W3020229432 modified "2023-10-13" @default.
• W3020229432 title "Zinc oxide nanoparticles modulate the gene expression of ZnT1 and ZIP8 to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells" @default.
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• W3020229432 doi "https://doi.org/10.1101/2020.04.22.055152" @default.
• W3020229432 hasPublicationYear "2020" @default.
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