Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Autor: Doumandji, Zahra, Safar, Ramia, Lovera-Leroux, Mélanie, Nahle, Sara, Cassidy, Hilary, Matallanas, David, Rihn, Bertrand, Ferrari, Luc, Joubert, Olivier
Přispěvatelé: Institut Jean Lamour (IJL), Université de Lorraine (UL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University College Dublin [Dublin] (UCD)
Rok vydání: 2019
Předmět:
Zdroj: Cell Biology and Toxicology
Cell Biology and Toxicology, Springer Verlag, 2020, 36 (1), pp.65-82. ⟨10.1007/s10565-019-09484-6⟩
ISSN: 0742-2091
1573-6822
DOI: 10.1007/s10565-019-09484-6
Popis: Metal oxide nanoparticles (NPs), such as ZnO, ZnFe2O4, and Fe2O3, are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe2O4, and Fe2O3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe2O4, and Fe2O3; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe2O4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC50 of ZnO and ZnFe2O4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe2O4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC50 of ZnO and ZnFe2O4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe2O4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe2O4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches. Electronic supplementary material The online version of this article (10.1007/s10565-019-09484-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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