Inhibition of ferroptosis protects House Ear Institute-Organ of Corti 1 cells and cochlear hair cells from cisplatin-induced ototoxicity.
Inhibition of ferroptosis protects House Ear Institute-Organ of Corti 1 cells and cochlear hair cells from cisplatin-induced ototoxicity.
复制标题
抑制铁死亡可保护 House Ear Institute-Corti 1 细胞和耳蜗毛细胞免受顺铂诱导的耳毒性
DOI：
10.1111/jcmm.15839
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发表时间：
2020-10
影响因子：
5.3
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Mei H;Zhao L;Li W;Zheng Z;Tang D;Lu X;He Y
铁凋亡症是最近认识到的一种非凋亡性细胞死亡形式，由脂质氢过氧化物的铁依赖性积累引起，在广泛的病理条件中起重要作用。本研究旨在研究铁凋亡对顺铂诱导的感觉毛细胞损伤的影响。通过细胞计数试剂盒-8和乳糖酶脱氢酶测定法测定细胞活力。通过2，7-二氯二氢荧光素二乙酸酯（DCFH-DA）和MitoSox-Red染色评价活性氧（ROS）水平。四甲基罗丹明甲酯（TMRM）染色测定线粒体膜电位（MMP）。分别通过Liperfluo、C11-BODIPY 581/591、FerroOrange和Mito-FerroGreen检测脂质过氧化、细胞内和线粒体铁。我们发现，顺铂治疗不仅显着增加ROS的积累，降低MMP，但增加脂质过氧化和铁积累的房子耳研究所器官的Corti 1（HEI-OC 1）细胞。值得注意的是，用特异性铁凋亡抑制剂ferrostatin-1治疗可以有效地消除顺铂诱导的毒性和随后的细胞死亡。具体而言，线粒体功能的改善是铁凋亡抑制剂对HEI-OC 1细胞中顺铂诱导的损伤的保护作用的重要机制。此外，抑制铁凋亡显着保护小鼠耳蜗毛细胞对顺铂的损害。此外，用铁凋亡诱导剂RSL 3处理小鼠耳蜗毛细胞显著加重顺铂诱导的损伤，这可以通过ROS抑制剂N-乙酰-L-半胱氨酸减轻。总的来说，我们的研究表明，铁凋亡抑制可以通过灭活脂质过氧化物自由基和改善毛细胞中的线粒体功能来减轻顺铂诱导的耳毒性。
Ferroptosis is a recently recognized form of non‐apoptotic cell death caused by an iron‐dependent accumulation of lipid hydroperoxides, which plays important roles in a wide spectrum of pathological conditions. The present study was aimed to investigate the impact of ferroptosis on cisplatin‐induced sensory hair cell damage. Cell viability was determined by Cell Counting Kit‐8 and lactase dehydrogenase assays. The reactive oxygen species (ROS) levels were evaluated by 2,7‐Dichlorodi‐hydrofluorescein diacetate (DCFH‐DA) and MitoSox‐Red staining. Mitochondrial membrane potential (MMP) was measured by tetramethylrhodamine methyl ester (TMRM) staining. Lipid peroxidation, intracellular and mitochondrial iron were detected by Liperfluo, C11‐BODIPY581/591, FerroOrange and Mito‐FerroGreen, respectively. We found that cisplatin treatment not only markedly augmented ROS accumulation, decreased the MMP, but increased lipid peroxidation and iron accumulation in House Ear Institute‐Organ of Corti 1 (HEI‐OC1) cells. Of note, treatment with the specific ferroptosis inhibitor ferrostatin‐1 could effectively abrogate the cisplatin‐induced toxicity and subsequent cell death. Specifically, the improvement of mitochondrial functions is important mechanisms for protective action of ferroptosis inhibitor against cisplatin‐induced damages in HEI‐OC1 cells. Moreover, inhibition of ferroptosis significantly protected murine cochlear hair cells against cisplatin damage. In addition, treatment murine cochlear hair cells with ferroptosis inducer, RSL3, significantly exacerbated cisplatin‐induced damage, which could be alleviated by ROS inhibitor N‐acetyl‐L‐cysteine. Collectively, our study indicated that ferroptosis inhibition could alleviate the cisplatin‐induced ototoxicity via inactivation of lipid peroxide radical and improvement of mitochondrial function in hair cells.
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影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
通讯作者：
Bayır H
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
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影响因子：
4.6
作者：
He Z;Cai C;Wang J;Xu X;Zheng P;Jetten MS;Hu B
通讯作者：
Hu B
影响因子：
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作者：
Ayala A;Muñoz MF;Argüelles S
通讯作者：
Argüelles S
影响因子：
2.2
作者：
Ghosh, Sharmila;Serafini, Rosanna;Varner, Dickson D.
通讯作者：
Varner, Dickson D.