Diphenyleneiodonium triggers the efflux of glutathione from cultured cells
Diphenyleneiodonium triggers the efflux of glutathione from cultured cells
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DOI：
10.1074/jbc.m111053200
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发表时间：
2002-05-31
影响因子：
4.8
通讯作者：
Hampton, MB
中科院分区：
文献类型：
--
作者：
Pullar, JM;Hampton, MB
二苯基碘鎓（DPI）是一种广谱黄素蛋白抑制剂，通常用于抑制吞噬细胞和非吞噬细胞的NADPH氧化酶产生氧化剂。先前的研究表明DPI可以使T24膀胱癌细胞对Fas介导的凋亡敏感。我们观察到DPI耗尽T24细胞和一系列其他原代和转化细胞类型中的细胞内还原型谷胱甘肽（GSH）。效果是立即的，与50%的细胞内GSH损失2小时内与DPI治疗。谷胱甘肽在细胞外介质中定量回收，表明正在发生外排。GSH的损失被阻断与溴磺酞，小管GSH转运的抑制剂。我们的结论是，DPI诱导细胞GSH从T24细胞通过一个特定的运输通道显着外流。这为它的促凋亡作用提供了一个潜在的机制，并且它对细胞中谷胱甘肽稳态的调节也具有重要意义。
Diphenyleneiodonium (DPI) is a broad-spectrum flavoprotein inhibitor commonly used to inhibit oxidant production by the NADPH oxidase of phagocytic and nonphagocytic cells. A previous study has shown that DPI can sensitize T24 bladder carcinoma cells to Fas-mediated apoptosis. We observed DPI to deplete intracellular reduced glutathione (GSH) in T24 cells and a range of other primary and transformed cell types. The effect was immediate, with 50% loss of intracellular GSH within 2 h of treatment with DPI. The glutathione was quantitatively recovered in the extracellular medium, indicating that efflux was occurring. The loss of GSH was blocked with bromosulfophthalein, an inhibitor of the canalicular GSH transporters. We conclude that DPI induces a dramatic efflux of cellular GSH from T24 cells via a specific transport channel. This provides a potential mechanism for its proapoptotic effect, and it also has important implications for the regulation of glutathione homeostasis in cells.