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A ratiometric fluorescent probe for real-time monitoring of intracellular glutathione fluctuations in response to cisplatin
Chemical Science ( IF 7.6 ) Pub Date : 2020-07-29 , DOI: 10.1039/d0sc02889d
Hanzhuang Liu 1, 2, 3, 4, 5 , Wenting Song 1, 2, 3, 4, 5 , Shuren Zhang 1, 2, 3, 4, 5 , Kin Shing Chan 1, 2, 3, 4, 5 , Zijian Guo 1, 2, 3, 4, 5 , Zhen Shen 1, 2, 3, 4, 5
Affiliation  

Real-time imaging of fluctuations in intracellular glutathione (GSH) concentrations is critical to understanding the mechanism of GSH-related cisplatin-resistance. Here, we describe a ratiometric fluorescence probe based on a reversible Michael addition reaction of GSH with the vinyl-functionalized boron-dipyrromethene (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene or BODIPY) 1. The probe was applied for real-time monitoring of the fluctuations in GSH levels in cells under cisplatin treatment. Notably, in cellular cisplatin-sensitive A549 cells, GSH concentrations rose until cell death, while in cisplatin-resistant cell lines, GSH levels first rose to the maximum then fell back to the initial concentration without significant apoptosis. These results indicate that different trends in GSH fluctuation can help distinguish cisplatin-resistant from cisplatin-sensitive cells. As such, this study has shown that probe 1 may potentially be used for real-time monitoring of intracellular GSH levels in response to therapeutics.

中文翻译:

用于实时监测细胞对顺铂反应中谷胱甘肽波动的比例荧光探针

实时成像的细胞内谷胱甘肽(GSH)浓度波动的成像对于了解GSH相关的顺铂耐药机制至关重要。在这里,我们描述了基于GSH的可逆迈克尔加成反应与乙烯基官能化硼-二吡咯亚甲基比例式荧光探针(4,4-二氟-4-硼-3-一个,4-diaza-小号-indacene或BODIPY)1个。该探针用于实时监测顺铂处理后细胞中GSH水平的波动。值得注意的是,在细胞对顺铂敏感的A549细胞中,GSH浓度上升直至细胞死亡,而在对顺铂耐药的细胞系中,GSH浓度首先上升到最大值,然后又回落到初始浓度,而没有明显的细胞凋亡。这些结果表明,GSH波动的不同趋势可以帮助区分顺铂耐药细胞和顺铂敏感细胞。因此,这项研究表明,探针1可能会潜在地用于响应治疗药物而实时监测细胞内GSH水平。
更新日期:2020-08-20
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