Unsymmetrically substituted polyamine analogue induces caspase-independent programmed cell death in Bcl-2-overexpressing cells.
Unsymmetrically substituted polyamine analogue induces caspase-independent programmed cell death in Bcl-2-overexpressing cells.
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发表时间：
1998-07
期刊：
影响因子：
11.2
通讯作者：
H. Ha;P. Woster;R. Casero
中科院分区：
文献类型：
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作者：
H. Ha;P. Woster;R. Casero
多胺类似物N1-乙基-N11-[（环庚基）甲基]-4，8-二氮杂十一烷（CHENSpm）在NCI H157细胞中诱导的程序性细胞死亡伴随有细胞色素c释放、线粒体膜电位损失、半胱天冬酶-3活化、半胱天冬酶介导的聚（ADP-核糖）聚合酶裂解、G2-M停滞以及DNA和核碎裂。Bcl-2的过表达完全抑制CHENSpm诱导的细胞色素c释放，半胱天冬酶-3活化和聚（ADP-核糖）聚合酶裂解。然而，Bcl-2并不消除CHENSpm诱导的程序性细胞死亡。这些结果表明，虽然细胞色素c的释放和激活的半胱天冬酶-3蛋白酶级联有助于细胞凋亡的快速和有效的执行，一个半胱天冬酶级联独立的途径也存在，并可以激活CHENSpm处理。
The polyamine analogue, N1-ethyl-N11-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm)-induced programmed cell death in NCI H157 cells is accompanied by cytochrome c release, the loss of mitochondrial membrane potential, activation of caspase-3, caspase-mediated poly(ADP-ribose) polymerase cleavage, G2-M arrest, and DNA and nuclear fragmentation. Overexpression of Bcl-2 completely inhibits CHENSpm-induced cytochrome c release, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage. However, Bcl-2 does not abrogate CHENSpm-induced programmed cell death. These results suggest that although cytochrome c release and activation of the caspase-3 protease cascade contribute to the rapid and efficient execution of apoptosis, a caspase cascade-independent pathway also exists and can be activated by CHENSpm treatment.