Ionizing radiation and the activation of caspase-8 in highly apoptosis-sensitive lymphoma cells.
OBJECTIVE
Ionizing radiation induces apoptosis in human lymphoma cells. However, the participating molecules and their exact order is unknown. Caspases are reported as essential cysteine proteases required for the activation and execution of programmed cell death. The activator caspase-8 is a key component of the CD95/Fas/APO-1 death receptor-triggered apoptosis pathway. Since contributing molecules for radiation-induced apoptosis and their exact order have not been analyzed in greater detail, the involvement of caspase-8 for radiation-induced apoptosis in human lymphoma cell lines was studied.


METHODS
Apoptosis induction by CD95 stimulation and ionizing radiation was analyzed in eight different cell lines. In parallel, Western blotting tested activation of caspase-8.


RESULTS
Activation of caspase-8 by ionizing radiation occurred in five cell lines and was associated with high apoptosis sensitivity. Caspase-8 activation and apoptosis was detectable in cells resistant to CD95 stimulation, so suggesting separate pathways for CD95 and radiation-induced caspase-8 activation.


CONCLUSIONS
The activator caspase-8 is activated during radiation-induced cell death and, in some cases, ionizing radiation induces caspase-8 independently of the CD95 system.
Belka
C
C
Department of Radiation Oncology, University of Tuebingen, Germany. claus.belka@uni-tuebingen.de
Heinrich
V
V
Marini
P
P
Faltin
H
H
Schulze-Osthoff
K
K
Bamberg
M
M
Budach
W
W
D017209:Apoptosis / Q000528:radiation effects*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation / Q000528:radiation effects; D006801:Humans; D008223:Lymphoma / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases