P53 transcription-independent activity mediates selenite-induced acute promyelocytic leukemia NB4 cell apoptosis
P53 transcription-independent activity mediates selenite-induced acute promyelocytic leukemia NB4 cell apoptosis
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DOI：
10.5483/bmbrep.2008.41.10.745
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发表时间：
2008-10-31
期刊：
影响因子：
3.8
通讯作者：
Xu, Caimin
中科院分区：
文献类型：
--
作者：
Guan, Liying;Huang, Fang;Xu, Caimin
硒是一种具有抗癌作用的必需微量元素，可诱导癌细胞凋亡。我们先前已经证明亚硒酸钠可以通过激活线粒体的凋亡途径来诱导NB4细胞的凋亡。然而，具体的机制仍不清楚。目前，我们证明了P53通过直接在线粒体上传递信号而参与了细胞凋亡。免疫荧光和Western印迹显示，亚硒酸盐诱导的P53易位到线粒体。抑制P53可阻断细胞内ROS的积聚和线粒体膜电位的丧失，提示线粒体P53作为ROS的上游信号，激活了线粒体的凋亡途径。亚硒还以一种ROS依赖的方式破坏细胞内钙离子的稳态，并增加线粒体钙离子浓度。P38激酶介导的P53的磷酸化和线粒体易位。综上所述，这些结果表明，P53通过易位到线粒体并以转录非依赖的方式激活线粒体凋亡通路，从而参与了亚硒诱导NB4细胞的凋亡。[BMB报告2008；41(10)：745-750]
Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. We have previously shown that sodium selenite can induce apoptosis by activating the mitochondrial apoptosis pathway in NB4 cells. However, the detailed mechanism remains unclear. Presently, we demonstrate that p53 contributes to apoptosis by directing signaling at the mitochondria. Immunofluorescent and Western blot procedures revealed selenite-induced p53 translocation to mitochondria. inhibition of p53 blocked accumulation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, suggesting that mitochondrial p53 acts as an upstream signal of ROS and activates the mitochondrial apoptosis pathway. Selenite also disrupted cellular calcium ion homeostasis in a ROS-dependent manner and increased mitochondrial calcium ion concentration. p38 kinase mediated phosphorylation and mitochondrial translocation of p53. Taken together, these results indicate that p53 involves selenite-induced NB4 cell apoptosis by translocation to mitochondria and activation mitochondrial apoptosis pathway in a transcription-independent manner. [BMB reports 2008; 41(10): 745-750]