Hydrogen Peroxide (H2O2) is one of many reactive oxygen species (ROS) that plays vital roles in intracellular signaling and stress processes, but its transient nature has made deciphering its roles in transcellular signaling a significant challenge. We have designed boronate caged small-molecule probes bearing a fluoromethylene pendant group that serves as a latent quinone methide source that can undergo a tandem activity-based sensing and biomolecule labeling reaction cascade to produce a spatially localized fluorescence signal upon exposure to H2O2. This strategy enables us to capture and record spatial information on ROS fluxes and has enabled us to move beyond studying intracellular H2O2 signaling to identifying and mapping cell-to-cell H2O2 communication in a microglia-neuron co-culture cell model, where selective activation of microglia for ROS production increases H2O2 in nearby neurons.
Support or Funding Information
This work was supported by the NIH (GM139245, ES28096, and ES4705 to C.J.C.) and by the UC Presidents Postdoctoral Fellowship Program, Chinook-Berkeley Postdoctoral Fellowship Program, and a NIH MOSAIC K99/R00 (1K99GM143573-01) awards to M.S.M.
This work was supported by the NIH (GM139245, ES28096, and ES4705 to C.J.C.) and by the UC Presidents Postdoctoral Fellowship Program, Chinook-Berkeley Postdoctoral Fellowship Program, and a NIH MOSAIC K99/R00 (1K99GM143573-01) awards to M.S.M.