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Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis

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Title: Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis
Authors: Hanagata, Nobutaka Browse this author →KAKEN DB
Zhuang, Fei Browse this author
Connolly, Sarah Browse this author
Li, Jie Browse this author
Ogawa, Nobuhiro Browse this author
Xu, Mingsheng Browse this author
Keywords: copper oxide nanoparticles
cytotoxicity
lung epithelial cells
cell cycle arrest
DNA microarray
Issue Date: Nov-2011
Publisher: American Chemical Society
Journal Title: ACS Nano
Volume: 5
Issue: 12
Start Page: 9326
End Page: 9338
Publisher DOI: 10.1021/nn202966t
Abstract: This study proposes a molecular mechanism for lung epithelial A549 cells response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3, and growth arrest and DNA damage-inducible 45 β and γ (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO-NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also induced by Cu ion concentrations higher than that released from CuO-NPs into medium, the expression appeared to be triggered by Cu ions released from CuO-NPs taken up into cells. We infer that for cells exposed to CuO-NPs, those able to make such a molecular response survived, and those unable to do so eventually died.
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright c2011 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/nn202966t
Type: article (author version)
URI: http://hdl.handle.net/2115/50888
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 花方 信孝

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