Rational Design of a Targetable Fluorescent Probe for Visualizing H₂S Production under Golgi Stress Response Elicited by Monensin

Abstract

As a eukaryotic organelle, the Golgi apparatus plays an essential role in various physiological activities such as stress response. The Golgi stress response is an important physiological process of conferring cytoprotection by regulating the synthesis and metabolism of bioactive molecules. Therefore, the development of new suitable in situ analytical techniques for monitoring related small molecular substances in the stress reaction of the Golgi apparatus is very helpful for further study of the regulatory mechanism of the Golgi apparatus. Recent studies have shown that endogenous hydrogen sulfide (H₂S) also possesses crucial bioregulatory and protective performances in the stress response. Therefore, the high-fidelity in situ mapping of H₂S production under the Golgi stress response plays an important role not only in revealing cytoprotection functions of H₂S in the stress response but also in further understanding the regulatory mechanism of the Golgi stress response. In this work, we designed a simple Golgi-targetable H₂S fluorescent probe (<b>Gol-H</b>_<b>2</b><b>S</b>) that responds accurately and sensitively to H₂S in the Golgi apparatus of living cells and zebrafish. On the basis of its superior bioimaging performances, probe <b>Gol-H</b>_<b>2</b><b>S</b> was successfully applied to the in situ visualization of H₂S production under the Golgi stress response elicited by monensin, a specific-Golgi stressor. The related process of the Golgi stress response was validated by stimulation and inhibition experiments. These findings fully demonstrate that H₂S is an alternative biomarker of the Golgi stress response. Moreover, probe <b>Gol-H</b>_<b>2</b><b>S</b> can also be used as a potential tool for disclosing the detailed H₂S-cytoprotection mechanisms under the regulation of the Golgi stress response in related diseases.