Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity
Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity
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DOI：
10.1016/j.yexcr.2005.02.023
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发表时间：
2005-07-01
影响因子：
3.7
通讯作者：
Watanabe, N
中科院分区：
文献类型：
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作者：
Furuya, D;Tsuji, N;Watanabe, N
Beclin 1被鉴定为Bcl-2相互作用蛋白，已知其可增强自噬。然而，Beclin I对细胞凋亡信号传导的作用仍不清楚。在这里，我们发现Beclin 1在MKN 28人胃癌细胞中的过表达增强了顺铂（CDDP）诱导的细胞凋亡。相反，在MKN 1细胞中通过小的抑制性RNA“敲低”Beclin 1减弱了这种细胞毒性。此外，经CDDP处理的Beclin I基因转染子中不仅caspase-3/7活性增加，而且caspase-9活性也增加，并且caspase-9抑制剂与caspase-3抑制剂一样完全消除了Beclin I对CDDP诱导的细胞凋亡的增强作用。因此，Beclin 1通过增强caspase-9活性增强CDDP诱导的细胞凋亡，并作为促凋亡分子发挥作用。(c)2005年爱思唯尔公司All rights reserved.
Beclin 1, identified as a Bcl-2-interacting protein, is known to enhance autophagy. However, the effect of Beclin I on apoptotic signaling has remained unclear. Here, we show that overexpression of Beclin 1 in MKN28 human gastric cancer cells augmented cis-diarnminedichloroplatinum (CDDP)-induced apoptosis. Conversely, "knockdown" of Beclin 1 by a small inhibitory RNA in MKN 1 cells attenuated this cytotoxicity. Furthermore, not only caspase-3/7 activities, but also caspase-9 activity was increased in Beclin I gene transfectants treated with CDDP, and caspase-9 inhibitor completely abolished augmentation of CDDP-induced apoptosis by Beclin I as did a caspase-3 inhibitor. Thus, Beclin 1 augments CDDP-induced apoptosis through enhancing caspase-9 activity and functions as a proapoptotic molecule. (c) 2005 Elsevier Inc. All rights reserved.