Gasotransmitter Regulation of Phosphatase Activity in Live Cells Studied by Three‐Channel Imaging Correlation

• Published in: Angewandte Chemie International Edition Vol. 58; no. 8; pp. 2261 - 2265
• Main Authors: Ou, Pan, Zhang, Ruilong, Liu, Zhengjie, Tian, Xiaohe, Han, Guangmei, Liu, Bianhua, Hu, Zhangjun, Zhang, Zhongping
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 18-02-2019
• Edition: International ed. in English
• Subjects: Correlation analysis; Dependence; Energy transfer; Enzymatic activity; Enzyme activity; enzyme regulation; Enzymes; Fluorescent indicators; fluorescent probes; Fluoroscopic imaging; gasotransmitters; Hydrogen sulfide; imaging agents; Phosphatase; Transmitters; phosphatase; gasotransmitters; imaging agents; enzyme regulation; fluorescent probes
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201811391

Enzyme activity in live cells is dynamically regulated by small‐molecule transmitters for maintaining normal physiological functions. A few probes have been devised to measure intracellular enzyme activities by fluorescent imaging, but the study of the regulation of enzyme activity via gasotransmitters in situ remains a long‐standing challenge. Herein, we report a three‐channel imaging correlation by a single dual‐reactive fluorescent probe to measure the dependence of phosphatase activity on the H2S level in cells. The two sites of the probe reactive to H2S and phosphatase individually produce blue and green fluorescent responses, respectively, and resonance energy transfer can be triggered by their coexistence. Fluorescent analysis based on the three‐channel imaging correlation shows that cells have an ideal level of H2S to promote phosphatase activity up to its maximum. Significantly, a slight deviation from this H2S level leads to a sharp decrease of phosphatase activity. The discovery further strengthens our understanding of the importance of H2S in cellular signaling and in various human diseases.
Two for one: A dual‐reactive molecular probe has been devised to simultaneously measure intracellular H2S levels and phosphatase activity. Fluorescent analysis by three‐channel imaging correlation reveals that a slight deviation from the normal H2S level leads to a sharp decrease of phosphatase activity.