Caspase-independent cell death without generation of reactive oxygen species in irradiated MOLT-4 human leukemia cells.
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.
Yoshida
Kengo
K
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan.
Kubo
Yoshiko
Y
Kusunoki
Yoichiro
Y
Morishita
Yukari
Y
Nagamura
Hiroko
H
Hayashi
Ikue
I
Kyoizumi
Seishi
S
Seyama
Toshio
T
Nakachi
Kei
K
Hayashi
Tomonori
T
D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology* / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects*; D048430:Cell Shape; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007938:Leukemia; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014965:X-Rays
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D017382:Reactive Oxygen Species; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; D020169:Caspases