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May 16-17, 2019 | Prague, Czech Republic
2
nd
International Conference on
22
nd
International Conference on
Nanomaterials and Nanotechnology
Advanced Nanoscience and Nanotechnology
Joint Event
&
Journal of Materials Science and Nanotechnology | Volume 3
Mater Sci Nanotechnol, Volume 3
Toxicity of metal oxides NP on rat macrophages: A combined transcriptomic and
proteomic study
Doumandji Zahra, Doumandji Z, Cassidy H, Gómez D, Safar R, Nahle S, Lovera-Leroux M, Schneider R, Alem-
Marchand H, Ferrari L, Rihn B H
and
Joubert O
Université de Lorraine, France
T
he paucity of biomarkers to predict the toxicity of
nanoparticles (NP) makes important to identify key
pathways linked to a toxic exposure of lung to NP. In this
study, we focused on the impacts of three metallic NP on
NR8383 alveolar macrophages to evaluate modifications in
transcriptome and proteome profiles after exposure to sub-
toxic doses of zinc oxide (ZnO), zinc ferrite oxide (ZnFe
2
O
4
),
and iron oxide (Fe
2
O
3
) NP. The cytotoxic potency of NP was
evaluated by extracellular LDH measurement and by WST1
assay. A significant induction of membrane damage and
reduction of NR8383 viability were noticed after 24 hours
exposure to the ZnO and ZnFe
2
O
4
NP. To understand the
interactions that occur and the biological consequences of
exposure of lung to NP, optimal conditions where NR8383
cells remained viable during the sub-toxic doses exposure.
Then, gene expression and protein production were
investigated by microarray profiles and mass spectrometry
methods, respectively. Genomic study showed 1036, 1274
and 3763 differentially expressed genes following 4 hours
exposure to sub-toxic doses of ZnO, ZnFe
2
O
4
and Fe
2
O
3
NP,
respectively. Proteomic study revealed 348, 784 and 872
differentially produced proteins after 24 hours, respectively.
Themain involvedpathways ingenomic studywereeIF2, eIF4/
p70S6K and protein ubiquitination signalings. Mitochondrial
dysfunction, oxidative phosphorylation, sirtuin signaling,
protein ubiquitination, unfolded protein response and
cholesterol biosynthesis were the main pathways affected
revealed by the proteomic study after exposure to the 3 NP.
The use of transcriptomic and proteomic platforms, with
appropriately designed experimental conditions, enabled the
observation of the early biological impairment induced by
ZnO, ZnFe
2
O
4
and Fe
2
O
3
NP. The data allowed us to suggest
that the protein synthesis default was the effect biomarker
for the three NP studied and the metallothioneins gene
overexpression was the exposure biomarker for zinc element.
e
:
zahra-manel.doumandji@univ-lorraine.fr