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
| Autor: | Pei-Shan Liu, Chien-Chang Huang, Lung Sen Kao, Chien-Yuan Pan, Fang-Yu Lin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
SH-SY5Y Physiology Cytotoxicity Gene Expression Metal Nanoparticles Apoptosis Toxicology Pathology and Laboratory Medicine Biochemistry Cell membrane 0302 clinical medicine Medicine and Health Sciences Homeostasis Enzyme assays Colorimetric assays Bioassays and physiological analysis Cation Transport Proteins chemistry.chemical_classification MTT assay Multidisciplinary Cell Death Chemistry Zinc medicine.anatomical_structure Cell Processes Physical Sciences Medicine Zinc Oxide Intracellular Research Article Chemical Elements inorganic chemicals Programmed cell death Cell Survival Science chemistry.chemical_element Transfection Research and Analysis Methods 03 medical and health sciences Lysosome Cell Line Tumor medicine Humans Molecular Biology Techniques Oxidopamine Molecular Biology Reactive oxygen species Biology and Life Sciences Biological Transport Cell Biology Molecular biology Cytosol Metabolism 030104 developmental biology chemistry Biochemical analysis biological sciences bacteria Physiological Processes Reactive Oxygen Species Zinc Transporters 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE, Vol 15, Iss 9, p e0232729 (2020) PLoS ONE |
| DOI: | 10.1101/2020.04.22.055152 |
| Popis: | Zinc ions (Zn2+) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn2+ concentration ([Zn2+]c), Zrt/Irt-related proteins (ZIPs) and Zn2+ transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the [Zn2+]c, respectively, by fluxing Zn2+ across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of [Zn2+]c and less investigate the [Zn2+]c at physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the [Zn2+]c to different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the [Zn2+]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 Zn2+ transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the [Zn2+]c transiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels of ZnT1 (mostly at the plasma membrane) and ZIP8 (present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of [Zn2+]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 [Zn2+]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. |
| Databáze: | OpenAIRE |
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