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

机译:Fascin2调节NRK-52E细胞中的顺铂诱导的细胞凋亡

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Previous studies have shown that the aging kidney has a marked loss of alpha(E)-catenin in proximal tubular epithelium. alpha-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 alpha(E)-catenin (C2 cells), as well as in aging (24 mon), but not young (4 mon), kidney. Fascin2 co-localized with alpha-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 alpha(E)-catenin, may play important role in preventing cisplatin-induced acute kidney injury. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
机译:以前的研究表明,老化肾脏在近端管状上皮中具有明显的α(e)-catenin的缺失。 Alpha-catenin是肌动蛋白细胞骨架的关键调节器,与各种肌动蛋白结合蛋白相互作用。在具有稳定敲低的α(e)-catenin(C2细胞)的细胞中观察到肌动蛋白2,肌动蛋白捆绑蛋白的损失,以及老化(24周期),但不是年轻(4周期),肾。 Fascin2与NRK-52E细胞中的α-catenin和actin细胞骨架共同定位。 Fascin2的敲低增加了管状上皮细胞对顺铂诱导的损伤的敏感性。 C2细胞中FASCIN2的过度表达恢复了肌动蛋白应激纤维,并减弱了C2细胞对顺铂诱导的细胞凋亡的提高敏感性。有趣的是,FASCIN2过表达衰减的顺铂诱导的线粒体功能障碍和C2细胞中的氧化应激。这些数据表明,Fascin2是α(e)-catenin的推定靶标,可能在预防顺铂诱导的急性肾损伤方面发挥重要作用。 (c)2016 Elsevier Ireland Ltd.保留所有权利。

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