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.

Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models

“…The clinical liver injury diagnostic methods are generally not suitable for the early assessment of liver injury. Since the pathogenesis of HIRI is closely related to oxidative stress disorder, − for example, previous evidence suggests that H 2 O 2 can activate the G-protein to destroy the junctional complex and enhance ischemia-reperfusion injury . In addition, distinct from other highly ROS (e.g., O 2 •– , • OH, ONOO – ) that are partially involved in ischemic damage, the stable H 2 O 2 is diffusible across the cell membrane, making it the main ROS that exacerbates ischemia-reperfusion injury.…”

A Reversible Fluorescent Probe for In Situ Monitoring Redox Imbalance during Mitophagy

“…Cellular redox balance is a prerequisite for normal physiological activities of cells . The redox imbalance in cells involves the occurrence and development of many diseases, such as cancer, degenerative disease, and arthritis. − In particular, mitochondria, as producers and sinks of intracellular reactive oxygen species (ROS), have a significant impact on the redox balance of cells. − Once mitochondria are damaged, mitophagy could be initiated and elimination of dysfunctional mitochondria in a lysosome-dependent manner, maintaining healthy mitochondrial population. , Mounting evidence suggests that many pathological processes could improve the intracellular ROS level to induce mitophagy. , Among these ROS, hydrogen peroxide (H 2 O 2 ) has broad actions in oxidative damaging and redox signaling. − Excessive mitochondrial H 2 O 2 may trigger mitophagy, which in turn reduces H 2 O 2 levels to protect cells. , Therefore, real-time imaging of the H 2 O 2 dynamic in mitochondria is vital to probe the redox imbalance during mitophagy.…”