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 is toxic at high concentrations. In mammalian cells, two copper transporters are known, CTR1 and CTR2. In order to gain insights on the possible influence of the import pathway on cellular responses to copper, two copper challenges were compared: one with copper ion, which is likely to use preferentially CTR1, and one with a copper-polyacrylate complex, which will be internalized via the endosomal pathway and is likely to use preferentially CTR2. A model system consisting in the J774A1 mouse macrophage system, with a strong endosomal/lysosomal pathway, was used. In order to gain wide insights into the cellular responses to copper, a proteomic approach was used. The proteomic results were validated by targeted experiments, and showed differential effects of the import mode on cellular physiology parameters.