Fluorescent Turn-On Probes for Visualizing GPx4 Levels in Live Cells and Predicting Drug Sensitivity

Glutathione peroxidase 4 (GPx4) is the membrane peroxidasein mammalsthat is essential for protecting cells against oxidative damage andcritical for ferroptosis. However, no live cell probe is currentlyavailable to specifically label GPx4. Herein, we report both inhibitoryand noninhibitory fluorescent turn-on probes for specific labelingof GPx4 in live cells. With these probes, the GPx4 expression levelsand degradation kinetics in live cells could be visualized, and theirreal-time responses to the cellular selenium availability were revealed.These probes could also potentially serve as staining reagents topredict the sensitivity of GPx4-related ferroptosis drugs. In viewof these features, these GPx4-selective probes will offer opportunitiesfor a deeper understanding of GPx4 function in natural habitats andhold great promise for biomedical applications.

Automated summary

We report the development of inhibitory and noninhibitory fluorescent turn-on probes for specific labeling of GPx4 in live cells. These probes allow visualization of GPx4 expression levels and degradation kinetics, and reveal the real-time response of GPx4 to cellular selenium availability. They also have potential applications in predicting the sensitivity of GPx4-related ferroptosis drugs.