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

Fiche publication

Date publication

février 2016

Journal

Journal of proteomics

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah , Dr VAN DORSSELAER Alain

Tous les auteurs :
Aude-Garcia C, Dalzon B, Ravanat JL, Collin-Faure V, Diemer H, Strub JM, Cianferani S, Van Dorsselaer A, Carrière M, Rabilloud T

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/26710724

Résumé

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.