https://scholars.lib.ntu.edu.tw/handle/123456789/573267
標題: | 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 | 作者: | Pan C.-Y Lin F.-Y Kao L.-S Huang C.-C Liu P.-S. CHIEN-YUAN PAN |
關鍵字: | messenger RNA; oxidopamine; protein Bax; protein bcl 2; protein p53; reactive oxygen metabolite; zinc oxide nanoparticle; cation transport protein; metal nanoparticle; reactive oxygen metabolite; SLC30A1 protein, human; zinc; zinc oxide; Zip8 protein, human; Article; blood brain barrier; cell membrane; controlled study; cytotoxicity; endosome; gene; gene expression; gene knockdown; human; human cell; incubation time; lysosome; MTT assay; oxidative stress; protein expression; real time polymerase chain reaction; SH-SY5Y cell line; zinc homeostasis; ZIP8 gene; ZnT1 gene; apoptosis; cell death; cell survival; drug effect; gene expression; metabolism; tumor cell line; Apoptosis; Cation Transport Proteins; Cell Death; Cell Line, Tumor; Cell Survival; Gene Expression; Humans; Metal Nanoparticles; Oxidopamine; Reactive Oxygen Species; Zinc; Zinc Oxide | 公開日期: | 2020 | 卷: | 15 | 期: | 9 | 來源出版物: | PLoS ONE | 摘要: | 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 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 (located 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. These results show that ZnO-NP-induced mild elevation in [Zn2 +]c activates beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurodegenerative diseases. Copyright: ? 2020 Pan et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090914708&doi=10.1371%2fjournal.pone.0232729&partnerID=40&md5=41d33cc6c061310383a28b5114041d84 https://scholars.lib.ntu.edu.tw/handle/123456789/573267 |
ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0232729 | SDG/關鍵字: | messenger RNA; oxidopamine; protein Bax; protein bcl 2; protein p53; reactive oxygen metabolite; zinc oxide nanoparticle; cation transport protein; metal nanoparticle; reactive oxygen metabolite; SLC30A1 protein, human; zinc; zinc oxide; Zip8 protein, human; Article; blood brain barrier; cell membrane; controlled study; cytotoxicity; endosome; gene; gene expression; gene knockdown; human; human cell; incubation time; lysosome; MTT assay; oxidative stress; protein expression; real time polymerase chain reaction; SH-SY5Y cell line; zinc homeostasis; ZIP8 gene; ZnT1 gene; apoptosis; cell death; cell survival; drug effect; gene expression; metabolism; tumor cell line; Apoptosis; Cation Transport Proteins; Cell Death; Cell Line, Tumor; Cell Survival; Gene Expression; Humans; Metal Nanoparticles; Oxidopamine; Reactive Oxygen Species; Zinc; Zinc Oxide |
顯示於: | 生命科學系 |
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