Copper(ii) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response

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Abstract

The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu released in cell culture medium suggested that Cu cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.
Original languageEnglish
Pages (from-to)7168-7184
Number of pages17
JournalNanoscale
Volume4
Issue number22
DOIs
Publication statusPublished - 21 Nov 2012

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Oxidative stress
Copper oxides
Cytotoxicity
Nanoparticles
Chemical activation
Transcription Factor AP-1
Toxicity
Poisons
Interleukins
Chemokines
Cell culture
Specific surface area
Small Interfering RNA
Culture Media
Cations
Reactive Oxygen Species
Suspensions
Raw materials
DNA
Hydrodynamics

Keywords

  • Chemokines
  • Copper
  • Heme Oxygenase-1
  • Hep G2 Cells
  • Humans
  • Interleukin-8
  • Interleukins
  • MAP Kinase Signaling System
  • Metal Nanoparticles
  • Mitogen-Activated Protein Kinase Kinases
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Oxidative Stress
  • RNA Interference
  • RNA, Small Interfering
  • Transcription Factor AP-1

Cite this

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title = "Copper(ii) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response",
abstract = "The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu released in cell culture medium suggested that Cu cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.",
keywords = "Chemokines, Copper, Heme Oxygenase-1, Hep G2 Cells, Humans, Interleukin-8, Interleukins, MAP Kinase Signaling System, Metal Nanoparticles, Mitogen-Activated Protein Kinase Kinases, NF-E2-Related Factor 2, NF-kappa B, Oxidative Stress, RNA Interference, RNA, Small Interfering, Transcription Factor AP-1",
author = "J.-P. Piret and D. Jacques and J.-N. Audinot and {Mejia Mendoza}, {Jorge Humberto} and E. Boilan and F. No{\"e}l and M. Fransolet and C. Demazy and S. Lucas and C. Saout and O. Toussaint",
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T1 - Copper(ii) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response

AU - Piret, J.-P.

AU - Jacques, D.

AU - Audinot, J.-N.

AU - Mejia Mendoza, Jorge Humberto

AU - Boilan, E.

AU - Noël, F.

AU - Fransolet, M.

AU - Demazy, C.

AU - Lucas, S.

AU - Saout, C.

AU - Toussaint, O.

PY - 2012/11/21

Y1 - 2012/11/21

N2 - The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu released in cell culture medium suggested that Cu cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.

AB - The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu released in cell culture medium suggested that Cu cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.

KW - Chemokines

KW - Copper

KW - Heme Oxygenase-1

KW - Hep G2 Cells

KW - Humans

KW - Interleukin-8

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KW - MAP Kinase Signaling System

KW - Metal Nanoparticles

KW - Mitogen-Activated Protein Kinase Kinases

KW - NF-E2-Related Factor 2

KW - NF-kappa B

KW - Oxidative Stress

KW - RNA Interference

KW - RNA, Small Interfering

KW - Transcription Factor AP-1

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SN - 2040-3364

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