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

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

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“…A cell lysis solution (Hepes 20 mM pH 7.5, MgCl2 2 mM, KCl 50 mM, tetradecyldimethylammonio propane sulfonate (SB 3-14) 0.15% w/v) was added at a ratio of 5 volumes of solution per volume of cell pellet, and the cells were left to lyse on ice for 20 minutes. The suspension was then centrifuged at 1000g for 5 minutes, the supernatant collected, and recentrifuged at 270,000g for 45 minutes to sediment the nanoparticles 58 .…”

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