Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells.
Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells.
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碘酸钠诱导人视网膜色素上皮 ARPE-19 细胞铁死亡
DOI：
10.1038/s41419-021-03520-2
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发表时间：
2021-03-03
影响因子：
9
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Liu B;Wang W;Shah A;Yu M;Liu Y;He L;Dang J;Yang L;Yan M;Ying Y;Tang Z;Liu K
碘酸钠（SI）是一种广泛使用的氧化剂，通过诱导视网膜色素上皮（RPE）细胞死亡来产生视网膜变性模型。然而，SI诱导RPE细胞死亡的机制仍不清楚。在本研究中，我们研究了经 SI 处理的培养的人视网膜色素上皮 (ARPE-19) 细胞的坏死特征，发现细胞凋亡或坏死性凋亡并不是主要的死亡途径。相反，死亡过程伴随着细胞内不稳定铁水平、ROS和脂质过氧化物的显着升高，这概括了铁死亡的关键特征。铁死亡抑制剂甲磺酸去铁胺 (DFO) 和铁他汀-1 (Fer-1) 部分阻止 SI 诱导的细胞死亡。进一步的研究表明，SI 处理不会改变 GPX4（谷胱甘肽过氧化物酶 4）的表达，但会导致还原硫醇基团的消耗，主要是细胞内 GSH（还原型谷胱甘肽）和半胱氨酸的消耗。铁运输研究表明，SI 处理并未改变铁流入量，但铁流出量增加，表明不稳定铁的增加可能是由于螯合铁的释放所致。这一假设得到了证实，SI 直接促进了无细胞裂解液中不稳定铁的释放。我们认为 SI 会消耗 GSH、增加 ROS、释放不稳定铁并增加脂质损伤，进而导致 ARPE-19 细胞铁死亡。
Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Instead, the death process was accompanied by significant elevation of intracellular labile iron level, ROS, and lipid peroxides which recapitulated the key features of ferroptosis. Ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1(Fer-1) partially prevented SI-induced cell death. Further studies revealed that SI treatment did not alter GPX4 (glutathione peroxidase 4) expression, but led to the depletion of reduced thiol groups, mainly intracellular GSH (reduced glutathione) and cysteine. The study on iron trafficking demonstrated that iron influx was not altered by SI treatment but iron efflux increased, indicating that the increase in labile iron was likely due to the release of sequestered iron. This hypothesis was verified by showing that SI directly promoted the release of labile iron from a cell-free lysate. We propose that SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells.
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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
影响因子：
7
作者：
Hanus J;Anderson C;Sarraf D;Ma J;Wang S
通讯作者：
Wang S
影响因子：
2.9
作者：
Epsztejn, S;Kakhlon, O;Cabantchik, ZI
通讯作者：
Cabantchik, ZI
影响因子：
9.7
作者：
Kim, Eun Hye;Shin, Daiha;Roh, Jong-Lyel
通讯作者：
Roh, Jong-Lyel
影响因子：
5.4
作者：
Hellinen, Laura;Pirskanen, Lea;Reinisalo, Mika
通讯作者：
Reinisalo, Mika