FIG. 2.
Schematic representation of P2X7R-mediated ROS production by NADPH oxidase. Activation of the P2X7R can promote ROS production by NADPH oxidases, a cell membrane complex consisting of several subunits. On assembly of these subunits in the membrane, this enzyme via its NOX2 (gp91phox) catalytic subunit generates a burst of ROS and activation of ASK1-p38 pathway. Activated P2X7Rs trigger NADPH oxidase activity by the translocation of NOX2 to plasma membrane, which is a critical step in the activation of the NADPH oxidase. This represents the major pathway for P2X7R-induced ROS formation. Calcium influx through P2X7R pore and mitochondrial overload could also mediate ROS production. Calcium can also stimulate NO synthase to generate NO, which enhances ROS production by mitochondria. It also appears that P2X7R activates ERK1/2/JNK1 pathways. These pathways trigger activation of various caspases, leading to changes in cellular functions. The best-characterized signaling downstream event of P2X7R activation is mediating the processing and release of IL-1β and IL-18. The P2X7R-induced and caspase-mediated cell apoptosis is also well established. ROS, reactive oxygen species; IL, interleukin.