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National Institute of Environmental Health Sciences

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Publication Detail

Title: A tandem activity-based sensing and labeling strategy enables imaging of transcellular hydrogen peroxide signaling.

Authors: Iwashita, Hidefumi; Castillo, Erika; Messina, Marco S; Swanson, Raymond A; Chang, Christopher J

Published In Proc Natl Acad Sci U S A, (2021 03 02)

Abstract: Reactive oxygen species (ROS) like hydrogen peroxide (H2O2) are transient species that have broad actions in signaling and stress, but spatioanatomical understanding of their biology remains insufficient. Here, we report a tandem activity-based sensing and labeling strategy for H2O2 imaging that enables capture and permanent recording of localized H2O2 fluxes. Peroxy Green-1 Fluoromethyl (PG1-FM) is a diffusible small-molecule probe that senses H2O2 by a boronate oxidation reaction to trigger dual release and covalent labeling of a fluorescent product, thus preserving spatial information on local H2O2 changes. This unique reagent enables visualization of transcellular redox signaling in a microglia-neuron coculture cell model, where selective activation of microglia for ROS production increases H2O2 in nearby neurons. In addition to identifying ROS-mediated cell-to-cell communication, this work provides a starting point for the design of chemical probes that can achieve high spatial fidelity by combining activity-based sensing and labeling strategies.

PubMed ID: 33622793 Exiting the NIEHS site

MeSH Terms: Animals; Boronic Acids/chemistry; Cell Communication; Cerebral Cortex/cytology; Cerebral Cortex/metabolism; Coculture Techniques; Embryo, Mammalian; Fluorescent Dyes/chemical synthesis; Fluorescent Dyes/metabolism*; HeLa Cells; Humans; Hydrogen Peroxide/metabolism*; Mice; Microglia/cytology; Microglia/drug effects; Microglia/metabolism*; Molecular Probes/chemical synthesis; Molecular Probes/metabolism*; Neurons/cytology; Neurons/drug effects; Neurons/metabolism*; Oxidation-Reduction; Paraquat/pharmacology; RAW 264.7 Cells; Signal Transduction/physiology*; Staining and Labeling/methods

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