Key Laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, P. R. China.
Research Institute of Applied Chemistry, Shanxi University, Taiyuan 030006, P. R. China.
J Am Chem Soc. 2020 Apr 1;142(13):6324-6331. doi: 10.1021/jacs.0c00992. Epub 2020 Mar 17.
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 (SO), 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 SO via an ICT-FRET synergetic mechanism. The probe shows completely reversed fluorescence responses toward GSH (enhanced red emission) and SO (annihilated red fluorescence) with high selectivity and sensitivity. In particular, the probe displayed completely different fluorescent signals (blue-shift) with SO in the presence of GSH, thereby allowing the imaging of the metabolism process of GSH to SO in two independent channels without spectral cross interference. Given these advantages, this probe has been successfully applied to the real-time monitoring of the SO metabolic process in living cells and mice models, and it has thus been found that GSH can metabolize SO by enzymatic reaction with TST (thiosulfate sulphurtransferase); additionally, SO was 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 SO in more biosystems.
谷胱甘肽 (GSH) 介导多种生物学事件和人类疾病。尽管近年来它一直是研究的热点，但由于缺乏适当的分析工具，其在活细胞中的分子机制和代谢途径仍知之甚少。二氧化硫 (SO) 是 GSH 的一种重要代谢物，通常与神经紊乱、心血管疾病和肺癌的症状有关。在此，我们通过 ICT-FRET 协同机制，合理设计并开发了一种新型多信号荧光探针，用于同时检测 GSH 及其代谢物 SO。该探针对 GSH（增强的红色发射）和 SO（红色荧光猝灭）具有高选择性和灵敏度，表现出完全相反的荧光响应。特别的是，在 GSH 存在的情况下，探针与 SO 表现出完全不同的荧光信号（蓝移），从而可以在两个独立的通道中对 GSH 到 SO 的代谢过程进行成像，而不会产生光谱交叉干扰。鉴于这些优势，该探针已成功应用于活细胞和小鼠模型中 SO 代谢过程的实时监测，结果表明 GSH 可以通过与 TST（硫代硫酸盐硫转移酶）的酶反应将 SO 代谢为硫酸盐；此外，SO 在 SUOX（亚硫酸盐氧化酶）的作用下转化为硫酸盐。我们预计，这项研究将为在更多生物系统中理解 GSH 和 SO 相互关联的生理功能提供一种方便、高效的工具。
