Differential regulation of apoptosis in AK‐5 tumor cells by the proto‐oncogene Bcl‐2: presence of Bcl‐2 dependent and independent pathways

FEBS Letters

Khar, Ashok¹  Anjum, Rana¹ 

[1] Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India

关键词: AK-5 cell;    Apoptosis;    Bcl-2;    Cytochrome c release;    zVAD-fmk;    z-Val-Ala-Asp fluoromethylketone;    PT;    permeability transition;    CCCP;    carbonylcyanide m-chlorophenylhydrazone;    Δψ m;    mitochondrial transmembrane potential;    DiOC6(3);    3′;    3′-dihexyloxacarbocyanine;   

DOI  :  10.1016/S0014-5793(01)02543-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown