Copper(II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response.
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(2+) released in cell culture medium suggested that Cu(2+) cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.
URBC, Namur Nanosafety Center (NNC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (FUNDP), 61 rue de Bruxelles, B-5000 Namur, Belgium. jppiret@fundp.ac.be
Jean-Pascal
JP
Piret
Diane
D
Jacques
Jean-Nicolas
JN
Audinot
Jorge
J
Mejia
Emmanuelle
E
Boilan
Florence
F
Noël
Maude
M
Fransolet
Catherine
C
Demazy
Stéphane
S
Lucas
Christelle
C
Saout
Olivier
O
Toussaint
D018925:Chemokines / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018925:Chemokines; D016209:Interleukin-8; D007378:Interleukins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D003300:Copper; D051547:Heme Oxygenase-1; D020929:Mitogen-Activated Protein Kinase Kinases; C030973:cupric oxide