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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

铁和阿霉素是活化线粒体通透性过渡孔的保护剂

卷 21, 期 6, 2021

发表于: 20 January, 2021

页: [514 - 525] 页: 12

弟呕挨: 10.2174/1568009621999210120192558

价格: $65

摘要

目标：本研究旨在检测铁、DOX及其复合物对线粒体通透性过渡孔(MPTP)开放的作用，并检测在接近线粒体依赖性铁垂的条件下MPTP可能的保护因子。 背景：阿霉素(DOX)的毒性主要与游离铁积累和线粒体功能障碍有关。DOX可引起铁下垂，由膜损伤引起的铁依赖细胞死亡。线粒体通透性过渡孔(MPTP)被认为是导致细胞凋亡、坏死和可能的铁下垂的共同途径。在铁存在的情况下，DOX对Ca2+诱导的MPTP开口的影响尚未研究。 目的：这项研究是在分离的肝脏和心脏线粒体上进行的。研究了MPTP和琥珀酸-泛素氧化还原酶作为DOX靶蛋白在线粒体依赖性铁弛缓症中的作用。铁螯合剂脱铁胺(DFO)、脂质自由基清除剂丁基-羟基甲苯(BHT)和钌红(Rr)可能是线粒体摄取亚铁离子的抑制剂，作为MPTP的保护剂。同时还考察了中碱化的作用。 方法：用Ca2+选择电极测量MPTP开放所需的阈值钙浓度的变化，用四苯基磷(TPP+)选择电极记录线粒体膜电位，并记录540 nm处的吸光度下降导致线粒体肿胀。通过还原琥珀酸脱氢酶(SDH)的电子受体DCPIP，测定其活性。 结论：MPTP和呼吸复合物II被确定为DOX对分离的线粒体铁依赖作用的主要靶点。所有的MPTP保护剂都可以消除或减弱铁和铁与DOX复合物对Ca2+诱导的MPTP开放的影响，在MPTP激活的不同阶段起作用。这些数据为调节DOX对线粒体的毒性影响提供了新的途径，目的是减少线粒体的功能障碍。

关键词: 阿霉素、铁、线粒体通透性过渡孔、丁羟甲苯、碱化、去铁胺

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图形摘要

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