Differential regulation of apoptosis in AK-5 tumor cells by the proto-oncogene Bcl-2: presence of Bcl-2 dependent and independent pathways.
FEBS Lett
; 499(1-2): 166-70, 2001 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-11418133
ABSTRACT
The anti-apoptotic protein Bcl-2 functions as a crucial negative regulator of apoptosis. Bcl-2 has been shown to prevent the efflux of apoptogenic factors from mitochondria to cytosol, thus inhibiting cell death. Here, we show the susceptibility of a spontaneously regressing, rat histiocytic tumor cell line, AK-5, to the apoptotic effects of diverse stimuli and the ability of Bcl-2 overexpression to block cell death. Bcl-2 overexpression selectively inhibits apoptosis induced by ceramide and serum factor from AK-5 tumor regressing animals but not actinomycin D and curcumin, whereas the pancaspase inhibitor z-Val-Ala-Asp fluoromethylketone completely blocks apoptosis, irrespective of the inducer used. The ability of Bcl-2 overexpression to block cell death does not depend on its ability to prevent cytochrome c release but correlates with its ability to prevent the dissipation of mitochondrial transmembrane potential. The results demonstrate that there are inducer dependent redundant activation pathways in a single cell, which may either be Bcl-2 dependent or independent.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Apoptose
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Genes bcl-2
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article