Proteasome inhibitors induce mitochondria-independent apoptosis in human glioma cells

被引:72
作者
Kitagawa, H
Tani, E
Ikemoto, H
Ozaki, I
Nakano, A
Omura, S
机构
[1] Hyogo Coll Med, Dept Neurosurg, Mol Biol Res Lab, Nishinomiya, Hyogo 6638501, Japan
[2] Kitasato Inst, Biol Funct Res Ctr, Tokyo 108, Japan
关键词
lactacystin; AcLLNal; caspase-3; cytochrome c; mitochondrial membrane potential; apoptosis; glioma;
D O I
10.1016/S0014-5793(98)01709-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The proteasome inhibitors lactacystin and AcLLNal induced p53-independent apoptosis in two human glioma cell Lines, and the apoptosis was accompanied by up-regulation of immunoreactive wild-type p53, p21(Waf1), Mdm2, and p27(Kip1). Pretreatment with cycloheximide decreased the induction of cell death independently bf p53 protein status, suggesting that the upregulation of short-lived proteins is associated with proteasome inhibitor-induced apoptosis, Caspase-3-like proteases were activated in the proteasome inhibitor-mediated apoptosis, and the induction of cell death was inhibited more effectively in the presence of z-VAD.fmk than in the presence of Ac-DEVD.fmk, suggesting that caspases other than caspase-3 are involved. Nonetheless, there were no significant alterations in levels of immunoreactive Bcl-2, Bcl-x(L), Bas, Bad, and Ball, nor ally evidence of cytochrome c release into cytosol and dissipation of Delta Psi(m). Thus, the proteasome inhibitor-induced apoptosis is mediated by a mitochondria-independent mechanism, and the once activated caspase-3 does not cause the cytochrome c release and the Delta Psi(m) disruption, (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:181 / 186
页数:6
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