Ferroptosis is a distinctive iron-dependent and GSH-related cell death form, and has been demonstrated to closely relate with Golgi apparatus (GA). Exploring the fluctuations of GSH level in GA during ferroptosis is of great importance for the deep research of biological functions of GA in ferroptosis. Herein, we reported a novel GA-targeting probe () for the detection of GSH in GA during ferroptosis. The probe utilized N-oxidized pyridine sulfonyl as a responsive site for GSH, with tetradecanoyl amide serving as GA-targeting moiety. exhibited remarkable sensitivity and selectivity, manifesting a heightened response to GSH and effectively visualizing GSH through bright green fluorescence under UV light. By fluorescence imaging of cellular GSH, was demonstrated to serve as a GA-targeting probe, and could successfully monitor the dynamic changes in intracellular GSH. Further experimentation revealed that NEM stimulation resulted in the removal of a significant amount of endogenous GSH in GA, and erastin-induced ferroptosis significantly reduced GSH levels in GA. Notably, we discovered that Fer-1 and VE effectively inhibited the substantial depletion of GSH in GA during ferroptosis.

中文翻译：

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开发高尔基体靶向探针以揭示铁死亡过程中活细胞中 GSH 的波动

铁死亡是一种独特的铁依赖性和谷胱甘肽相关的细胞死亡形式，并已被证明与高尔基体（GA）密切相关。探究GA在铁死亡过程中GSH水平的波动对于深入研究GA在铁死亡中的生物学功能具有重要意义。在此，我们报道了一种新型 GA 靶向探针 ()，用于检测铁死亡期间 GA 中的 GSH。该探针利用 N-氧化吡啶磺酰基作为 GSH 的响应位点，并用十四酰酰胺作为 GA 靶向部分。表现出卓越的灵敏度和选择性，表现出对 GSH 的增强响应，并在紫外光下通过亮绿色荧光有效地可视化 GSH。通过细胞GSH的荧光成像，证明其可以作为GA靶向探针，并且可以成功监测细胞内GSH的动态变化。进一步的实验表明，NEM刺激导致GA中大量内源性GSH的去除，而erastin诱导的铁死亡显着降低了GA中的GSH水平。值得注意的是，我们发现 Fer-1 和 VE 有效抑制铁死亡期间 GA 中 GSH 的大量消耗。