Fas-independent apoptosis induced by UVC in p53-mutated human epithelial tumor A431 cells through activation of caspase-8 and JNK/SAPK.
J Radiat Res
; 42(2): 201-15, 2001 Jun.
Article
em En
| MEDLINE
| ID: mdl-11599886
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
/
Apoptose
/
Receptor fas
/
Caspases
/
Quinases de Proteína Quinase Ativadas por Mitógeno
/
Proteínas Quinases JNK Ativadas por Mitógeno
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article