Fascin2 regulates cisplatin-induced apoptosis in NRK-52E cells.

Fascin2 regulates cisplatin-induced apoptosis in NRK-52E cells.
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DOI:
10.1016/j.toxlet.2016.11.021
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发表时间:
2017-01-15
期刊:
影响因子:
3.5
通讯作者:
Parrish AR
Parrish AR
中科院分区:
医学3区
文献类型:
--
作者:
Wang X;Nichols L;Grunz-Borgmann EA;Sun Z;Meininger GA;Domeier TL;Baines CP;Parrish AR

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先前的研究表明,衰老的肾脏近端肾小管上皮细胞中α(E)-连环蛋白明显丢失。α-连环蛋白是肌动蛋白细胞骨架的关键调节因子,与多种肌动蛋白结合蛋白相互作用。在α(E)-连环蛋白稳定敲低的细胞(C2细胞)以及衰老(24个月)肾脏中观察到顺铂诱导的fascin 2(一种肌动蛋白捆绑蛋白)丢失,但在年轻(4个月)肾脏中未观察到。在NRK-52 E细胞中,Fascin 2与α-catenin和肌动蛋白细胞骨架共定位。敲低fascin 2增加了肾小管上皮细胞对顺铂诱导的损伤的易感性。Fascin 2在C2细胞中的过表达恢复了肌动蛋白应力纤维,并减弱了C2细胞对顺铂诱导的凋亡的敏感性。有趣的是,fascin 2过表达减弱了顺铂诱导的C2细胞线粒体功能障碍和氧化应激。这些数据表明,fascin 2,α(E)-catenin的推定目标,可能在预防顺铂诱导的急性肾损伤中发挥重要作用。
Previous studies have shown that the aging kidney has a marked loss of α(E)-catenin in proximal tubular epithelium. α-Catenin, a key regulator of the actin cytoskeleton, interacts with a variety of actin-binding proteins. Cisplatin-induced loss of fascin2, an actin bundling protein, was observed in cells with a stable knockdown of α(E)-catenin (C2 cells), as well as in aging (24 mon), but not young (4 mon), kidney. Fascin2 co-localized with α-catenin and the actin cytoskeleton in NRK-52E cells. Knockdown of fascin2 increased the susceptibility of tubular epithelial cells to cisplatin-induced injury. Overexpression of fascin2 in C2 cells restored actin stress fibers and attenuated the increased sensitivity of C2 cells to cisplatin-induced apoptosis. Interestingly, fascin2 overexpression attenuated cisplatin-induced mitochondrial dysfunction and oxidative stress in C2 cells. These data demonstrate that fascin2, a putative target of α(E)-catenin, may play important role in preventing cisplatin-induced acute kidney injury.
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