Figure 21.

Comparison of two types of cell death, necrosis and apoptosis (adapted from Ref. 100). The cell death by PARP activation described in Section 4 is thought to occur through necrosis. In apoptotic cell death, PARP is cleaved by caspases and inactivated. Therefore, PARP inhibitors can be effective in preventing necrosis but ineffective in preventing apoptosis. “Whether to die from necrosis or to die from apoptosis” may depend on the severity and duration of the cell damage, differences in death signals, and the species of cells. A report from Bhardwaj’s laboratory suggests that dendritic cells distinguish between two types of cell death, with necrosis providing a control that is critical for the initiation of immunity.²⁸³⁾ Therefore, immunological abnormalities, which are frequently observed in Type 1 diabetes, may be triggered by the preceding necrotic cell death, and then cause apoptotic death of β-cells (see also Fig. 22).