Alpha-Lipoic Acid Attenuates Apoptosis and Ferroptosis in Cisplatin-Induced Ototoxicity via the Reduction of Intracellular Lipid Droplets.
Alpha-Lipoic Acid Attenuates Apoptosis and Ferroptosis in Cisplatin-Induced Ototoxicity via the Reduction of Intracellular Lipid Droplets.
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α-硫辛酸通过减少细胞内脂滴来减轻顺铂诱导的耳毒性中的细胞凋亡和铁死亡。
DOI：
10.3390/ijms231810981
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发表时间：
2022-09-19
影响因子：
5.6
通讯作者：
Kim, Sung Kyun
中科院分区：
文献类型：
--
作者：
Cho, Sam;Hong, Seok Jin;Kang, Sung Hun;Park, YongKeun;Kim, Sung Kyun
α-硫辛酸（α-LA）是一种有效的抗氧化剂，可通过ROS阻止顺铂诱导的耳毒性相关的细胞凋亡。铁凋亡症被定义为最近被强调的铁依赖性细胞死亡途径，并且与由于炎症过程引起的细胞内脂滴（LD）的积累相关。在此，我们研究了α-LA对铁凋亡的影响，并使用高分辨率三维定量相位成像结合折射率（RI）分布重建分析了顺铂处理的听毛细胞中LD的特征。用500 μM α-LA处理HEI-OC 1细胞24 h，然后用15 μM顺铂处理48 h。利用三维光学衍射断层成像（3D-ODT）分析处理后细胞的RI值。具有高RI值的区域被认为是LD，并标记以测量LD的计数、质量和体积。通过蛋白质印迹法评估LC 3-B、P62、GPX 4、4-羟基壬烯醛（4-HNE）和xCT的表达。顺铂损伤的HEI-OC 1细胞显示脂质过氧化、xCT耗竭和4-HNE异常蓄积。此外，细胞中LD的数量、质量和体积增加。经α-LA处理的细胞抑制4-HNE的表达，而xCT和GPX 4的表达得以恢复，这使LD恢复到与对照组相似的水平。我们对LD的3D-ODT研究提供了铁凋亡的生物学证据，并为研究分子途径的其他方法提供了见解。
Alpha-lipoic acid (α-LA) is a potent antioxidant that can prevent apoptosis associated with cisplatin-induced ototoxicity through ROS. Ferroptosis is defined as an iron-dependent cell death pathway that has recently been highlighted and is associated with the accumulation of intracellular lipid droplets (LDs) due to an inflammatory process. Herein, we investigated the impact of α-LA on ferroptosis and analyzed the characteristics of LDs in auditory hair cells treated with cisplatin using high-resolution 3D quantitative-phase imaging with reconstruction of the refractive index (RI) distribution. HEI-OC1 cells were treated with 500 μM α-LA for 24 h and then with 15 μM cisplatin for 48 h. With 3D optical diffraction tomography (3D-ODT), the RI values of treated cells were analyzed. Regions with high RI values were considered to be LDs and labelled to measure the count, mass, and volume of LDs. The expression of LC3-B, P62, GPX4, 4-hydroxynonenal (4-HNE), and xCT was evaluated by Western blotting. HEI-OC1 cells damaged by cisplatin showed lipid peroxidation, depletion of xCT, and abnormal accumulation of 4-HNE. Additionally, the count, mass, and volume of LDs increased in the cells. Cells treated with α-LA had inhibited expression of 4-HNE, while the expression of xCT and GPX4 was recovered, which restored LDs to a level that was similar to that in the control group. Our research on LDs with 3D-ODT offers biological evidence of ferroptosis and provides insights on additional approaches for investigating the molecular pathways.
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