Fas-independent apoptosis induced by UVC in p53-mutated human epithelial tumor A431 cells through activation of caspase-8 and JNK/SAPK.
A431 cells/UVC-induced apoptosis/Caspase 8/Fas/JNK/PAPK. We previously observed that p53-mutated human epithelial tumor A431 cells underwent apoptosis after ultraviolet C (UVC) irradiation through the caspases-8 and -3 pathway. Fas/FasL is known to initiate apoptosis in several cell lines via caspase-8 activation. Then, to determine if Fas/FasL mediates apoptosis in A431. we investigated Fas expression and modulation in UVC-irradiated A431 cells. A431 constitutively expressed Fas, which gradually decreased after UVC-irradiation. Pretreatment with a neutralizing anti-Fas antibody, ZB4, did not abrogate the UVC-induced apoptosis. An agonistic anti-Fas antibody, CH11, very slowly induced apoptosis in A431. suggesting that the constitutively expressed Fas had a low functional potential. Hence, UVC-induced apoptosis in A431 seems to occur independent of the Fas signal. Interestingly, however, a pretreatment with CH11 remarkably potentiated UVC-induced apoptosis. An inhibitor of caspase-8, Ac-IETD-CHO, partially inhibited UVC-induced apoptosis. JNK was phosphorylated immediately after exposure to UVC. prior to apoptotic chromatin condensation. Our data suggest that the activation of caspase-8 occurs independent of Fas upregulation, and that JNK/ SAPK contributes to UVC-induced apoptosis in human epithelial A431 cells.
Hama-Inaba
H
H
Radiation Hazards Research Group, National Institute of Radiological Sciences, Chiba, Japan.
Choi
K H
KH
Wang
B
B
Haginoya
K
K
Yamada
T
T
Hayata
I
I
Ohyama
H
H
D017209:Apoptosis / Q000528:radiation effects*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009154:Mutation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000032:analysis*
D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases