Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
Tempo, a nitroxide, exerts an SOD-like antioxidant activity against ROS. Reportedly, Tempo inhibits ROS-induced apoptosis in thymocytes, and activates JNK1 to induce apoptosis in breast cancer cells. In this present study, we observed sensitization of heat-induced apoptosis by 5 mM Tempo in the pheochromocytoma cell line (PC12). We investigated the sensitization mechanisms. 5 mM Tempo or 44C/10 min heating was non-apoptotic to PC12 cells. However, the combined treatment markedly sensitized PC12 cells to apoptosis, as induced by 44C/30 min. Although levels of Bcl-2, Bcl-XL and Bax in lysates were not altered, Bax was rapidly translocated to mitochondria after the combined treatment and 44C/30 min, followed by cytochrome c release. The combined treatment and 44C/30 min activated JNK 1, which was partially inhibited by the inhibitors of JNK. Our results suggest that sensitization of Tempo/heat-induced apoptosis may involve Bax-mediated increase in outer mitochondrial membrane permeability resulting in cytochrome c release.
