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

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.