17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha
17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha
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17-β 雌二醇通过雌激素受体 α 抑制氧化应激诱导的 AIF 积累到核仁和 PARP1 依赖性细胞死亡
DOI：
10.1016/j.toxlet.2014.09.024
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发表时间：
2015-01-05
影响因子：
3.5
通讯作者：
Ba, Xueqing
中科院分区：
文献类型：
--
作者：
Batnasan, Enkhzaya;Wang, Ruoxi;Ba, Xueqing
氧化应激诱导的DNA损伤导致聚（ADP-核糖）聚合酶1（PARP 1）过度活化，导致parthanatos，一种新发现的细胞消除途径。PARP 1依赖性细胞死亡的抑制已显示出改善疾病的结果，包括中风、心脏缺血和神经退行性疾病。在本研究中，我们旨在检测雌激素是否在抑制parthanatos中起保护作用。我们利用了大量表达雌激素受体α和β（ER α和ER β）的人乳腺癌细胞（MCF 7）。通过用过氧化氢（H2 O2）攻击细胞来诱导Parthanatos。进行了显微成像和分子生物学技术，如Western印迹分析和RNA干扰。结果表明，17 β雌二醇（E2）通过降低蛋白质PAR化和AIF易位到核/核仁中来保护MCF 7细胞免于PARP 1依赖的细胞死亡。在E2加入前通过siRNA下调ERa表达导致E2介导的H2 O2诱导的蛋白PAR化和AIF核仁易位的抑制失败。总之，这些数据表明，雌激素通过其α型受体抑制氧化应激诱导的PARP 1依赖性细胞死亡。本研究为我们提供了如何将激素治疗应用于与parthanatos相关的缺血性和退行性疾病的干预的见解。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Oxidative stress-induced DNA damage results in over-activation of poly(ADP-ribose) polymerase 1 (PARP1), leading to parthanatos, a newly discovered cell elimination pathway. Inhibition of PARP1-dependent cell death has shown to improve the outcome of diseases, including stroke, heart ischemia, and neurodegenerative diseases. In the present study we aimed to detect whether estrogen plays a protective role in inhibiting parthanatos. We utilized human mammary adenocarcinoma cells (MCF7) that abundantly express the estrogen receptor alpha and beta (ER alpha and ER beta). Parthanatos was induced by challenging the cells with hydrogen peroxide (H2O2). Microscopic imaging and molecular biological techniques, such as Western blot analysis and RNA interference, were performed. The results showed 17 beta estradiol (E2) protected MCF7 cells from PARP1-dependent cell death by decreasing protein PARylation, and AIF translocation into nuclei/nucleoli. Down-regulation of ERa expression by siRNA before E2 addition resulted in the failure of the E2-mediated inhibition of H2O2-induced protein PARylation and AIF nucleolar translocation. Together these data suggest that estrogen via its alpha-type receptor inhibits oxidative stress-induced, PARP1-dependent cell death. The present study provided us insight into how to apply hormone therapy in intervention of parthanatos-implicated ischemic and degenerative diseases. (C) 2014 Elsevier Ireland Ltd. All rights reserved.