A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

被引：43

作者：

Aude-Garcia, Catherine ^{[1
,2
,3
]}

Dalzon, Bastien ^{[1
,2
,3
]}

Ravanat, Jean-Luc ^{[4
,5
]}

Collin-Faure, Veronique ^{[1
,2
,3
]}

Diemer, Helene ^{[6
,7
]}

Strub, Jean Marc ^{[6
,7
]}

Cianferani, Sarah ^{[6
,7
]}

Van Dorsselaer, Alain ^{[6
,7
]}

Carriere, Marie ^{[4
,5
]}

Rabilloud, Thierry ^{[1
,2
,3
]}

机构：

[1] CEA Grenoble, IRTSV CBM, Lab Chem & Biol Met, F-38000 Grenoble, France

[2] Univ Grenoble Alpes, Lab Chem & Biol Met, F-38000 Grenoble, France

[3] CNRS, UMR 5249, Lab Chem & Biol Met, Grenoble, France

[4] Univ Grenoble Alpes, INAC, SCIB, F-38000 Grenoble, France

[5] CEA Grenoble, INAC SCIB LAN, F-38000 Grenoble, France

[6] Univ Strasbourg, IPHC, LSMBO, 25 Rue Becquerel, F-67087 Strasbourg, France

[7] CNRS, UMR7178, F-67037 Strasbourg, France

来源：

JOURNAL OF PROTEOMICS | 2016年 / 134卷

关键词：

Nanoparticles; Macrophages; Zinc oxide; Zirconium dioxide; Proteomics; Glutathione biosynthesis; Phagocytosis; DNA damage; Heme oxygenase; Methyglyoxal; Mitochondria; ARYL-HYDROCARBON RECEPTOR; IMMOBILIZED PH GRADIENTS; OXIDATIVE STRESS; 2-DIMENSIONAL ELECTROPHORESIS; SILVER NANOPARTICLES; TIO2; NANOPARTICLES; CELL-CULTURE; BOVINE HEART; AH RECEPTOR; DNA-DAMAGE;

D O I：

10.1016/j.jprot.2015.12.013

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The cellular responses of the J774 macrophage cell line to zinc oxide and zirconium oxide nanoparticles have been studied by a comparative quantitative, protein level based proteomic approach. The most prominent results have been validated by targeted approaches. These approaches have been carried out under culture conditions that stimulate mildly the aryl hydrocarbon receptor, thereby mimicking conditions that can be encountered in vivo in complex environments. The comparative approach with two nanoparticles allows to separate the common responses, which can be attributed to the phagocytosis event per se, from the response specific to each type of nanoparticles. The zinc-specific responses are the most prominent ones and include mitochondrial proteins too, but also signaling molecules such as MyD88, proteins associated with methylglyoxal detoxification (glyoxalase 2, aldose reductase) and deoxyribonucleotide hydrolases. The in cellulo inhibition of GAPDH by zinc was also documented, representing a possible source of methylglyoxal in the cells, leading to an increase in methylglyoxal-modified DNA bases. These observations may be mechanistically associated with the genotoxic effect of zinc and its selective effects on cancer cells. Biological significance: The responses of the murine J774 macrophage cell lines to two types of metallic oxide nanoparticles (zinc oxide and zirconium dioxide) were studied by a comparative 2D gel based approach. This allows sorting of shared responses from nanoparticle-specific responses. Zinc oxide nanoparticles induced specifically a strong decrease in the mitochondrial function, in phagocytosis and also an increase in the methylglyoxal-associated DNA damage, which may explain the well known genotoxicity of zinc. In conclusion, this study allows highlighting of pathways that may play an important role in the toxicity of the zinc oxide nanoparticles. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：174 / 185

页数：12

共 89 条

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