The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 Apoptotic Signaling Pathway

Figure 6

LPS stimulated cells to induce the P2X7R-mediated intracellular Omi/HtrA2 apoptosis signaling pathway. Under the stress stimulation of LPS, mitochondria in cells will produce a large amount of ATP and activate P2X7R on the cell surface. The activated P2X7R will cause a large amount of Ca2+ influx, and then the imbalance of intracellular Ca2+ homeostasis will lead to the production of a large amount of intracellular ROS and further cause mitochondrial damage. However, Ca2+ overload in mitochondria will further increase the production of ROS and cause the transfer of OMI/HtrA2 in the damaged mitochondrial membrane space into the cytoplasm. Omi/HtrA2 in the cytoplasm can crack the apoptosis inhibiting protein XIAP, which leads to the decrease of XIAP inhibiting caspase-3 and caspase-9 in cells, and promotes cell apoptosis.