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Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells
Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society of Toxicology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354944/ https://www.ncbi.nlm.nih.gov/pubmed/30766660 http://dx.doi.org/10.5487/TR.2019.35.1.083 |
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author | Kim, Dong-Yung Kim, Jun-Hyung Lee, Jae-Chul Won, Moo-Ho Yang, Se-Ran Kim, Hyoung-Chun Wie, Myung-Bok |
author_facet | Kim, Dong-Yung Kim, Jun-Hyung Lee, Jae-Chul Won, Moo-Ho Yang, Se-Ran Kim, Hyoung-Chun Wie, Myung-Bok |
author_sort | Kim, Dong-Yung |
collection | PubMed |
description | Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ≥ 15 μg/mL, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures. |
format | Online Article Text |
id | pubmed-6354944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Korean Society of Toxicology |
record_format | MEDLINE/PubMed |
spelling | pubmed-63549442019-02-14 Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells Kim, Dong-Yung Kim, Jun-Hyung Lee, Jae-Chul Won, Moo-Ho Yang, Se-Ran Kim, Hyoung-Chun Wie, Myung-Bok Toxicol Res Original Article Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ≥ 15 μg/mL, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures. Korean Society of Toxicology 2019-01 2018-01-15 /pmc/articles/PMC6354944/ /pubmed/30766660 http://dx.doi.org/10.5487/TR.2019.35.1.083 Text en Copyright © 2019 The Korean Society Of Toxicology http://creativecommons.org/licenses/by-nc/3.0 This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Dong-Yung Kim, Jun-Hyung Lee, Jae-Chul Won, Moo-Ho Yang, Se-Ran Kim, Hyoung-Chun Wie, Myung-Bok Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells |
title | Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells |
title_full | Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells |
title_fullStr | Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells |
title_full_unstemmed | Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells |
title_short | Zinc Oxide Nanoparticles Exhibit Both Cyclooxygenase- and Lipoxygenase-Mediated Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells |
title_sort | zinc oxide nanoparticles exhibit both cyclooxygenase- and lipoxygenase-mediated apoptosis in human bone marrow-derived mesenchymal stem cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354944/ https://www.ncbi.nlm.nih.gov/pubmed/30766660 http://dx.doi.org/10.5487/TR.2019.35.1.083 |
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