Yoshida Kengo, Kubo Yoshiko, Kusunoki Yoichiro, Morishita Yukari, Nagamura Hiroko, Hayashi Ikue, Kyoizumi Seishi, Seyama Toshio, Nakachi Kei, Hayashi Tomonori
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan.
Cell Immunol. 2009;255(1-2):61-8. doi: 10.1016/j.cellimm.2008.10.006. Epub 2008 Dec 9.
To improve our understanding of ionizing radiation effects on immune cells, we investigated steps leading to radiation-induced cell death in MOLT-4, a thymus-derived human leukemia cell. After exposure of MOLT-4 cells to 4 Gy of X-rays, irradiated cells sequentially showed increase in intracellular reactive oxygen species (ROS), decrease in mitochondrial membrane potential, and eventually apoptotic cell death. In the presence of the caspase inhibitor z-VAD-fmk, irradiated cells exhibited necrotic characteristics such as mitochondrial swelling instead of apoptosis. ROS generation was not detected during this necrotic cell death process. These results indicate that radiation-induced apoptosis in MOLT-4 cells requires elevation of intracellular ROS as well as activation of a series of caspases, whereas the cryptic necrosis program--which is independent of intracellular ROS generation and caspase activation--is activated when the apoptosis pathway is blocked.
为了增进我们对电离辐射对免疫细胞影响的理解，我们研究了源自胸腺的人类白血病细胞MOLT-4中辐射诱导细胞死亡的相关步骤。将MOLT-4细胞暴露于4 Gy的X射线后，受辐照细胞依次出现细胞内活性氧（ROS）增加、线粒体膜电位降低，最终发生凋亡性细胞死亡。在存在半胱天冬酶抑制剂z-VAD-fmk的情况下，受辐照细胞表现出坏死特征，如线粒体肿胀而非凋亡。在这种坏死性细胞死亡过程中未检测到ROS生成。这些结果表明，MOLT-4细胞中辐射诱导的凋亡需要细胞内ROS升高以及一系列半胱天冬酶的激活，而当凋亡途径被阻断时，独立于细胞内ROS生成和半胱天冬酶激活的隐匿性坏死程序会被激活。
