A novel Golgi-targetable fluorescent probe for imaging peroxynitrite in Golgi stress and sepsis-induced acute lung injury

Abstract

The Golgi apparatus is a crucial component of the endomembrane system and is involved in various physiological and pathological processes. Recently, increasing evidence shows that Golgi participates in oxidative stress in sepsis-induced acute lung injury (ALI). As a kind of reactive oxygen species (ROS), peroxynitrite (ONOO−) plays a significant role in a range of oxidative stress-related diseases. Therefore, accurately monitoring the level of ONOO− in the Golgi apparatus is crucial for revealing the mechanism of Golgi ONOO− in the sepsis-induced ALI. Unfortunately, no such probe has been reported to detect Golgi ONOO− in sepsis-induced ALI model. In this work, a Golgi-targetable probe FC-ONOO was designed and synthesized for high sensitivity and selectivity monitoring ONOO− generation during the Golgi stress response in sepsis-induced ALI model. The probe displayed high sensitivity (about 57 nM of detection limit) and good selectivity towards ONOO−. Additionally, it was successfully applied in mapping the increase of ONOO− levels in the Golgi of live cells induced by different stimuli. More importantly, the substantial increases in ONOO− levels in the Golgi apparatus were observed in the sepsis-induced ALI of mice for the first time. Given all its outstanding advantages, it has great potential for application in other ONOO− related diseases.