Fig. 6

Overview of SiNPs-induced apoptotic and necrotic cell death pathways independently in HUVECs. The 20-nm SiNP exposed to the membrane of endothelial cells, leading to intracellular ROS level. NADPH oxidase (NOX), a non-mitochondrial source of ROS increase, generates superoxide anions through oxygen reduction mediated by the electron donor NADPH. NOX-derived ROS contribute ER stress and activate unfolded protein response (UPR), resulting that IRE1α dissociated from BiP responses the unfolded proteins. Subsequently, the resultant trans-autophosphorylation induce apoptotic cell death. In addition, 20-nm SiNP induce autophagy activation, independent of ROS, via PI3K/AKT/eNOS/nitric oxide signaling pathway. Under the induction of autophagy, RIP1 interacts with RIP3 to form complex Iib, which is involved in necroptosis. As a result, autophagy induced by 20-nm SiNP causes necrotic cell death