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Proteomic Analyses Reveal that Sky1 Modulates Apoptosis and Mitophagy in Saccharomyces cerevisiae Cells Exposed to Cisplatin

机译:蛋白质组学分析显示Sky1调节暴露于顺铂的酿酒酵母细胞中的凋亡和线粒体。

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摘要

Sky1 is the only member of the SR (Serine–Arginine) protein kinase family in Saccharomyces cerevisiae. When yeast cells are treated with the anti-cancer drug cisplatin, Sky1 kinase activity is necessary to produce the cytotoxic effect. In this study, proteome changes in response to this drug and/or SKY1 deletion have been evaluated in order to understand the role of Sky1 in the response of yeast cells to cisplatin. Results reveal differential expression of proteins previously related to the oxidative stress response, DNA damage, apoptosis and mitophagy. With these precedents, the role of Sky1 in apoptosis, necrosis and mitophagy has been evaluated by flow-cytometry, fluorescence microscopy, biosensors and fluorescence techniques. After cisplatin treatment, an apoptotic-like process diminishes in the ∆sky1 strain in comparison to the wild-type. The treatment does not affect mitophagy in the wild-type strain, while an increase is observed in the ∆sky1 strain. The increased resistance to cisplatin observed in the ∆sky1 strain may be attributable to a decrease of apoptosis and an increase of mitophagy.
机译:Sky1是酿酒酵母(SR-Serine-Arginine)蛋白激酶家族的唯一成员。当用抗癌药顺铂处理酵母细胞时,Sky1激酶活性对于产生细胞毒性作用是必需的。在这项研究中,已评估了响应此药物和/或SKY1缺失的蛋白质组变化,以了解Sky1在酵母细胞对顺铂反应中的作用。结果揭示了以前与氧化应激反应,DNA损伤,细胞凋亡和线粒体相关的蛋白质的差异表达。有了这些先例,已经通过流式细胞仪,荧光显微镜,生物传感器和荧光技术评估了Sky1在细胞凋亡,坏死和线粒体中的作用。与野生型相比,顺铂处理后,∆sky1株的凋亡样过程减少。该处理方法不影响野生型菌株的线粒体吞噬,而∆sky1菌株中的线粒体吞噬能力却有所提高。在sky1菌株中观察到的对顺铂耐药性的增加可能归因于细胞凋亡的减少和线粒体的增加。

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