CREB-mediated Bcl-2 expression in trichosanthin-induced Hela cell apoptosis.

CREB-mediated Bcl-2 expression in trichosanthin-induced Hela cell apoptosis.
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DOI:
10.1016/j.bbrc.2007.08.141
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发表时间:
2007-11
影响因子:
3.1
通讯作者:
Ping Wang;Hui Yan;Jicheng Li
Ping Wang;Hui Yan;Jicheng Li
中科院分区:
生物学4区
文献类型:
--
作者:
Ping Wang;Hui Yan;Jicheng Li

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在天花粉蛋白(TCS)诱导的细胞凋亡过程中,bcl2在细胞死亡的调控中起着关键作用。由于Bcl2的表达受转录因子cAMP反应元件结合蛋白(CREB)的调控,因此我们研究了CREB的激活在TCS诱导Hela细胞凋亡中的作用。我们的结果表明,天花粉蛋白诱导的Hela细胞凋亡伴随着Bcl2和磷酸化CREB蛋白水平的降低。有趣的是,这种抑制作用可以通过TCS/cAMP激动剂的联合治疗而取消。此外,通过反义处理抑制CREB的表达,并用Cre诱骗寡核苷酸阻断CREB结合蛋白与Bcl2环状AMP反应元件(Cre)之间的相互作用,从而取消了TCS介导的Bcl2蛋白。因此,这些数据支持CREB在天花粉蛋白诱导的Hela细胞死亡中对Bcl2表达的调节起关键作用的假说。
Bcl-2 plays a pivotal role in the control of cell death and is down-regulated in trichosanthin (TCS)-induced cell apoptosis. Because Bcl-2 expression is regulated by the transcription factor cyclic AMP response element-binding protein (CREB), we investigated the role of CREB activation in TCS-induced Hela cells apoptosis. Our results showed that TCS-caused Hela cell apoptosis was accompanied by the decrease of Bcl-2 and phosphorylated CREB protein levels. Interesting, this inhibitive effect can be abolished by the combined treatment of TCS/cAMP agonists. Furthermore, TCS-mediated Bcl-2 protein was abrogated by the suppression of CREB expression with antisense treatment, and blocking the interaction between CREB-binding protein and the Bcl-2 cyclic AMP-responsive element (CRE) by a CRE decoy oligonucleotide. Therefore, these data support the hypothesis that CREB plays a critical role in the regulation of Bcl-2 expression in TCS-induced Hela cell death.