Beclin 1通过增强半胱天冬酶-9的活性增强顺二氯二氨铂诱导的细胞凋亡。

Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity.

作者信息

Furuya Daisuke, Tsuji Naoki, Yagihashi Atsuhito, Watanabe Naoki

机构信息

Department of Clinical Laboratory Medicine, Sapporo Medical University, School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.

出版信息

Exp Cell Res. 2005 Jul 1;307(1):26-40. doi: 10.1016/j.yexcr.2005.02.023. Epub 2005 Mar 31.

DOI:10.1016/j.yexcr.2005.02.023

PMID:15922724

Abstract

Beclin 1, identified as a Bcl-2-interacting protein, is known to enhance autophagy. However, the effect of Beclin 1 on apoptotic signaling has remained unclear. Here, we show that overexpression of Beclin 1 in MKN28 human gastric cancer cells augmented cis-diamminedichloroplatinum (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 1 gene transfectants treated with CDDP, and caspase-9 inhibitor completely abolished augmentation of CDDP-induced apoptosis by Beclin 1 as did a caspase-3 inhibitor. Thus, Beclin 1 augments CDDP-induced apoptosis through enhancing caspase-9 activity and functions as a pro-apoptotic molecule.

摘要

Beclin 1被鉴定为一种与Bcl-2相互作用的蛋白，已知其可增强自噬作用。然而，Beclin 1对凋亡信号传导的影响仍不清楚。在此，我们发现，在MKN28人胃癌细胞中过表达Beclin 1可增强顺二氯二氨铂（CDDP）诱导的凋亡。相反，在MKN 1细胞中用小干扰RNA“敲低”Beclin 1可减弱这种细胞毒性。此外，在用CDDP处理的Beclin 1基因转染细胞中，不仅半胱天冬酶-3/7活性增加，半胱天冬酶-9活性也增加，并且半胱天冬酶-9抑制剂与半胱天冬酶-3抑制剂一样，完全消除了Beclin 1对CDDP诱导凋亡的增强作用。因此，Beclin 1通过增强半胱天冬酶-9活性来增强CDDP诱导的凋亡，并作为一种促凋亡分子发挥作用。