Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles.
Fiche publication
Date publication
février 2020
Journal
Cell biology and toxicology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr RIHN Bertrand
Tous les auteurs :
Doumandji Z, Safar R, Lovera-Leroux M, Nahle S, Cassidy H, Matallanas D, Rihn B, Ferrari L, Joubert O
Lien Pubmed
Résumé
Metal oxide nanoparticles (NPs), such as ZnO, ZnFeO, and FeO, 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, ZnFeO, and FeO in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFeO, and FeO; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFeO 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 IC of ZnO and ZnFeO 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 ZnFeO 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 IC of ZnO and ZnFeO 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 ZnFeO NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFeO NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.
Mots clés
Iron oxide nanoparticles, NR8383, Proteomics, Transcriptomics, Zinc iron oxide nanoparticles, Zinc oxide nanoparticles
Référence
Cell Biol Toxicol. 2020 02;36(1):65-82