A tandem activity-based sensing and labeling strategy enables imaging of transcellular hydrogen peroxide signaling
- 23 February 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (9)
- https://doi.org/10.1073/pnas.2018513118
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.Funding Information
- HHS | NIH | National Institute of General Medical Sciences (GM139245)
- HHS | NIH | National Institute of Environmental Health Sciences (ES28096)
- HHS | NIH | National Institute of Environmental Health Sciences (ES4705)
- U.S. Department of Veterans Affairs (1IO1 BX004884)
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