Near-Infrared Fluorescence Probe for in Situ Detection of Superoxide Anion and Hydrogen Polysulfides in Mitochondrial Oxidative Stress

摘要

H2S plays important physiological and pathological roles in the cardiovascular system and nervous system. However, recent evidence imply that hydrogen polysulfides (H2Sn) are the actual signaling molecules in cells. Although H2Sn have been demonstrated to be responsible for mediating tumor suppressors, ion channels, and transcription factors, more of their biological effects are still need to be elaborated. On one hand, H2S have been suggested to be generated from endogenous H2S upon reaction with reactive oxygen species (ROS). On the other hand, H2S derivatives are proposed to be a kind of direct antioxidant against intracellular oxidative stress. This conflicting results should be attributed to the regulation of redox homeostasis between ROS and H2Sn. Superoxide anion (O-2(center dot-) is undoubtedly the primary ROS existing in mitochondria. We reason that the balance of O-2(center dot-) and H2S are pivotal in physiological and pathological processes. Herein, we report two near-infrared fluorescent probes Hcy-Mito and Hcy-Biot for the detection of O-2(center dot-) and H2S, in cells and in vivo. Hcy-Mito is conceived to be applied in mitochondria, and Hcy-Biot is designed to target tumor tissue. Both of the probes were successfully applied for visualizing exogenous and endogenous O-2(center dot-) and H2Sn in living cells and in tumor mice models. The results demonstrate that H2Sn can be promptly produced by mitochondrial oxidative stress. Flow cytometry assays for apoptosis suggest that H2Sn play critical roles in antioxidant systems.