A proteomic view of cellular responses of macrophages to copper when added as ion or as copper-polyacrylate complex

Copper is an essential metal for life, but toxic at high concentrations. In mammalian cells, two copper transporters are known, CTR1 and CTR2. order to gain insights on the possible influence of import pathway cellular responses copper, challenges were compared: one with ion, which likely use preferentially CTR1, a copper-polyacrylate complex, will be internalized via endosomal A model system consisting in J774A1 mouse macrophage system, strong endosomal/lysosomal pathway, was used. wide into proteomic approach The results validated by targeted experiments, showed differential effects mode physiology parameters. While mitochondrial transmembrane potential kept constant, depletion free glutahione content observed (ion polylacrylate complex). Both polyacrylate induced perturbations cytoskeleton phagocytosis. Inflammatory also differently altered ion copper-polyacrylate. Copper-polyacrylate perturbed several metabolic enzymes. Lastly, enzymes used as test set assess predictive value proteomics. Proteomic profiling provides depth analysis alterations cells under different exposure modes this metal, namely or complex polyacrylate. substantially between modes, although some shared, such glutathione. Targeted experiments confirm results. Some activities after complex. basal inflammatory while forms inhibited lipopolysaccharide-induced responses.