Fig. 15.

Mechanism of bystander signaling of tumor cells after treatment with H₂O₂ and nitrite. Continuation. A. Secondary singlet oxygen (#1, #4) causes inactivation of catalase on the original cell (# 2, #5) or on neighbouring cells (#3, #7), or activates the FAS receptor on neighbouring cells (#6). As a consequence, the generation of secondary singlet oxygen is activated within the cell population (#8 - #10) in an autoamplificatory mode. B. After sufficient inactivation of catalase in the cell population (#1) H₂O₂ generated through dismutation of NOX1-derived superoxide anions (#2) is no longer decomposed and is used as substrate by peroxidase (POD) (#3) for the generation of HOCl (#4). The reaction between HOCl and superoxide anions (#5) yields hydroxyl radicals (#6) in close vicinity to the membrane. This results in lipid peroxidation (#7) and the subsequent induction of the mitochondrial pathway of apoptosis (#8). For simplicity, it is not shown that apoptosis induction by lipid peroxidation requires a preceding influx of H₂O₂ through aquaporins that lowers the intracellular gluatathione level.