Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis
Erastin induces ferroptosis via ferroportin-mediated iron accumulation in endometriosis
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DOI：
10.1093/humrep/deaa363
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发表时间：
2021-04-01
影响因子：
6.1
通讯作者：
Gao, Ying
中科院分区：
文献类型：
--
作者：
Li, Yajie;Zeng, Xinliu;Gao, Ying
研究问题：erastin是否能激活铁下垂，使增生性病变消退？总结回答：Erastin可诱导铁凋亡，使子宫内膜异位症的病变消退。已知：异位子宫内膜基质细胞（EESC）处于铁超载的微环境中，对氧化损伤更敏感。erastin-induced ferroptosis的特点是铁依赖性积累的致命脂质活性氧（ROS）。研究设计，规模，持续时间：11例无子宫内膜异位症和21例子宫内膜异位症患者被招募在这项研究中。原代正常和异位子宫内膜间质细胞的分离，培养和进行各种处理。体内实验采用10只C57 BL/6雌性小鼠建立子宫内膜异位症模型。对象/材料、地点、方法：采用细胞活力、脂质过氧化水平和形态学改变等指标检测子宫内膜铁凋亡的指标。采用比色法测定细胞活力，流式细胞仪测定脂质过氧化水平，透射电镜观察细胞形态学变化。免疫组化和western blot检测FPN的表达。普鲁士蓝染色和免疫荧光显微镜催化亚铁半定量铁的水平。采用腺病毒介导的FPN过表达和siRNA介导的FPN敲低技术研究FPN在erastin诱导的EESC铁凋亡中的作用。主要结果和机会作用：与正常子宫内膜基质细胞（NESC）相比，EESC对erastin处理更敏感（P
STUDY QUESTION: Could erastin activate ferroptosis to regress endometriotic lesions?SUMMARY ANSWER: Erastin could induce ferroptosis to regress endometriotic lesions in endometriosis.WHAT IS KNOWN ALREADY: Ectopic endometrial stromal cells (EESCs) are in an iron overloading microenvironment and tend to be more sensitive to oxidative damage. The feature of erastin-induced ferroptosis is iron-dependent accumulation of lethal lipid reactive oxygen species (ROS).STUDY DESIGN, SIZE, DURATION: Eleven patients without endometriosis and 21 patients with endometriosis were recruited in this study. Primary normal and ectopic endometrial stromal cells were isolated, cultured and subjected to various treatments. The in vivo study involved 10 C57BL/6 female mice to establish the model of endometriosis.PARTICIPANTS/MATERIALS, SETTING, METHODS: The markers of ferroptosis were assessed by cell viability, lipid peroxidation level and morphological changes. The cell viability was measured by colorimetric method, lipid peroxidation levels were measured by flow cytometry, and morphological changes were observed by transmission electron microscopy. Immunohistochemistry and western blot were used to detect ferroportin (FPN) expression. Prussian blue staining and immunofluorescent microscopy of catalytic ferrous iron were semi-quantified the levels of iron. Adenovirus-mediated overexpression and siRNA-mediated knockdown were used to investigate the role of FPN on erastin-induced ferroptosis in EESCs.MAIN RESULTS AND THE ROLE OF CHANCE: EESCs were more susceptible to erastin treatment, compared to normal endometrial stromal cells (NESCs) (P