Employing an ICT-FRET Integration Platform for the Real-Time Tracking of SO2 Metabolism in Cancer Cells and Tumor Models
Employing an ICT-FRET Integration Platform for the Real-Time Tracking of SO2 Metabolism in Cancer Cells and Tumor Models
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采用 ICT-FRET 集成平台实时跟踪癌细胞和肿瘤模型中的 SO2 代谢
DOI：
10.1021/jacs.0c00992
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发表时间：
2020
影响因子：
15
通讯作者：
Caixia Yin
中科院分区：
文献类型：
--
作者：
Weijie Zhang;Fangjun Huo;Fangqin Cheng;Caixia Yin
谷胱甘肽（GSH）介导多种生物学事件和人类疾病。虽然近年来它一直是深入研究的主题，但由于缺乏适当的分析工具，对其在活细胞中的分子机制和代谢途径的进一步了解仍然有限。二氧化硫（SO2）是谷胱甘肽的重要代谢产物，通常与神经系统疾病、心血管疾病和肺癌的症状有关。因此，我们设计并开发了一种新型的多信号荧光探针，通过ICT-FRET协同机制同时检测GSH及其代谢产物SO2。该探针对GSH（增强的红色发射）和SO2（湮灭的红色荧光）显示完全相反的荧光响应，具有高选择性和灵敏度。特别是，在GSH存在下，该探针显示与SO2完全不同的荧光信号（蓝移），从而允许在两个独立通道中成像GSH到SO2的代谢过程，而没有光谱交叉干扰。该探针已成功应用于活细胞和小鼠模型中SO2代谢过程的实时监测，发现GSH可通过与硫代硫酸盐硫转移酶（TST）的酶促反应代谢SO2，并且SO2在亚硫酸盐氧化酶（SUOX）的作用下转化为硫酸盐。本研究为进一步了解GSH和SO2在更多生物系统中的相互作用提供了一个方便、有效的工具。
Glutathione (GSH) mediates a wide variety of biological events and human diseases. Although it has been the subject of intense study in recent years, a further understanding of its molecular mechanisms and metabolism routes in living cells has remained limited due to a lack of appropriate analytical tools. Sulfur dioxide (SO2), an important metabolite of GSH, is usually associated with the symptoms of neurological disorders, cardiovascular diseases, and lung cancer. Herein, a novel multisignal fluorescent probe was rationally designed and exploited for the simultaneous detection of GSH and its metabolite SO2via an ICT-FRET synergetic mechanism. The probe shows completely reversed fluorescence responses toward GSH (enhanced red emission) and SO2(annihilated red fluorescence) with high selectivity and sensitivity. In particular, the probe displayed completely different fluorescent signals (blue-shift) with SO2in the presence of GSH, thereby allowing the imaging of the metabolism process of GSH to SO2in two independent channels without spectral cross interference. Given these advantages, this probe has been successfully applied to the real-time monitoring of the SO2metabolic process in living cells and mice models, and it has thus been found that GSH can metabolize SO2by enzymatic reaction with TST (thiosulfate sulphurtransferase); additionally, SO2was transformed into sulfate under SUOX (sulfite oxidase). We anticipate that this research will provide a convenient and efficient tool for understanding the interrelated physiological functions of GSH and SO2in more biosystems.