Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach.
Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.
Univ. Grenoble Alpes, Laboratory of Chemistry and Biology of Metals, UMR CNRS-CEA-UJF 5249, iRTSV/LCBM, CEA Grenoble, 17 rue des martyrs, F-38054 Grenoble Cedex 9, France. thierry.rabilloud@cea.fr.
Sarah
S
Triboulet
Catherine
C
Aude-Garcia
Lucie
L
Armand
Adèle
A
Gerdil
Hélène
H
Diemer
Fabienne
F
Proamer
Véronique
V
Collin-Faure
Aurélie
A
Habert
Jean-Marc
JM
Strub
Daniel
D
Hanau
Nathalie
N
Herlin
Marie
M
Carrière
Alain
A
Van Dorsselaer
Thierry
T
Rabilloud
D000818:Animals; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D005978:Glutathione / Q000378:metabolism; D007477:Ions / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D020543:Proteome / Q000032:analysis / Q000187:drug effects; D015032:Zinc / Q000737:chemistry*; D015034:Zinc Oxide / Q000737:chemistry*
D007477:Ions; D020543:Proteome; D005978:Glutathione; D015032:Zinc; D015034:Zinc Oxide