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

Metal oxide nanoparticles (NPs), such as ZnO, ZnFe(2)O(4), and Fe(2)O(3), 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-t...

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Autores principales: Doumandji, Zahra, Safar, Ramia, Lovera-Leroux, Mélanie, Nahle, Sara, Cassidy, Hilary, Matallanas, David, Rihn, Bertrand, Ferrari, Luc, Joubert, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051947/
https://www.ncbi.nlm.nih.gov/pubmed/31352547
http://dx.doi.org/10.1007/s10565-019-09484-6
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author Doumandji, Zahra
Safar, Ramia
Lovera-Leroux, Mélanie
Nahle, Sara
Cassidy, Hilary
Matallanas, David
Rihn, Bertrand
Ferrari, Luc
Joubert, Olivier
author_facet Doumandji, Zahra
Safar, Ramia
Lovera-Leroux, Mélanie
Nahle, Sara
Cassidy, Hilary
Matallanas, David
Rihn, Bertrand
Ferrari, Luc
Joubert, Olivier
author_sort Doumandji, Zahra
collection PubMed
description Metal oxide nanoparticles (NPs), such as ZnO, ZnFe(2)O(4), and Fe(2)O(3), 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, ZnFe(2)O(4), and Fe(2)O(3) in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC(50) were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe(2)O(4), and Fe(2)O(3); global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe(2)O(4) 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(50) of ZnO and ZnFe(2)O(4) 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 ZnFe(2)O(4) 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(50) of ZnO and ZnFe(2)O(4) 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 ZnFe(2)O(4) NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe(2)O(4) 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.
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spelling pubmed-70519472020-03-16 Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles Doumandji, Zahra Safar, Ramia Lovera-Leroux, Mélanie Nahle, Sara Cassidy, Hilary Matallanas, David Rihn, Bertrand Ferrari, Luc Joubert, Olivier Cell Biol Toxicol Original Article Metal oxide nanoparticles (NPs), such as ZnO, ZnFe(2)O(4), and Fe(2)O(3), 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, ZnFe(2)O(4), and Fe(2)O(3) in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC(50) were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe(2)O(4), and Fe(2)O(3); global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe(2)O(4) 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(50) of ZnO and ZnFe(2)O(4) 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 ZnFe(2)O(4) 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(50) of ZnO and ZnFe(2)O(4) 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 ZnFe(2)O(4) NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe(2)O(4) 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. Springer Netherlands 2019-07-27 2020 /pmc/articles/PMC7051947/ /pubmed/31352547 http://dx.doi.org/10.1007/s10565-019-09484-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Doumandji, Zahra
Safar, Ramia
Lovera-Leroux, Mélanie
Nahle, Sara
Cassidy, Hilary
Matallanas, David
Rihn, Bertrand
Ferrari, Luc
Joubert, Olivier
Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
title Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
title_full Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
title_fullStr Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
title_full_unstemmed Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
title_short Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
title_sort protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051947/
https://www.ncbi.nlm.nih.gov/pubmed/31352547
http://dx.doi.org/10.1007/s10565-019-09484-6
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