Uncovering Endoplasmic Reticulum Superoxide Regulating Hepatic Ischemia-Reperfusion Injury by Dynamic Reversible Fluorescence Imaging

Abstract

Hepatic ischemia-reperfusion injury (HIRI) is a relatively common complication of liver resection and transplantation that is intimately connected to oxidative stress. The superoxide anion radical (O₂^•-), as the first reactive oxygen species produced by organisms, is an important marker of HIRI. The endoplasmic reticulum (ER) is an essential site for O₂^•- production, especially ER oxidative stress, which is closely linked to HIRI. Thus, dynamic variations in ER O₂^•- may accurately indicate the HIRI extent. However, there is still a lack of tools for the dynamic reversible detection of ER O₂^•-. Therefore, we designed and prepared an ER-targeted fluorescent reversible probe DPC for real-time tracing of O₂^•- fluctuations. We successfully observed a marked increase in ER O₂^•- levels in HIRI mice. A potential NADPH oxidase 4-ER O₂^•--SERCA2b-caspase 4 signaling pathway in HIRI mice was also revealed. Attractively, DPC was successfully used for precise fluorescent navigation and excision of HIRI sites.