Figure 3.

a) Principle of ZnO nanoparticle‐induced the apoptosis/necrosis of RGC‐5 cells. Reproduced with permission.170 Copyright 2013, Elsevier. b) Schematic illustration of putative calcium signaling pathway in RGC5 cell death induced by ZnO nanoparticles. The scheme illustrates the possible pathway of intracellular calcium ion elevation mediated by plasma membrane calcium ATPases. Because of exposure to ZnO nanoparticles, the Ca²⁺‐ATPase activity is inhibited, leading to influx of extracellular calcium and elevation of intracellular calcium ion level, then mitochondria produce excessive ROS. The excessive ROS can also decrease the production of PMCA2 at gene and protein levels, inhibit the Ca²⁺‐ATPase activity, and further aggravate the disrupted intracellular calcium homeostasis, finally initiate the cellular apoptosis/necrosis. ER = endoplasmic reticulum. Reproduced with permission.171 Copyright 2013, Elsevier.