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Visualizing peroxynitrite fluxes in endothelial cells reveals the dynamic progression of brain vascular injury.

Abstract
Accumulating evidence suggests that formation of peroxynitrite (ONOO(-)) in the cerebral vasculature contributes to the progression of ischemic damage, while the underlying molecular mechanisms remain elusive. To fully understand ONOO(-) biology, efficient tools that can realize the real-time tracing of endogenous ONOO(-) fluxes are indispensable. While a few ONOO(-) fluorescent probes have been reported, direct visualization of ONOO(-) fluxes in the cerebral vasculature of live mice remains a challenge. Herein, we present a fluorescent switch-on probe (NP3) for ONOO(-) imaging. NP3 exhibits good specificity, fast response, and high sensitivity toward ONOO(-) both in vitro and in vivo. Moreover, NP3 is two-photon excitable and readily blood-brain barrier penetrable. These desired photophysical and pharmacokinetic properties endow NP3 with the capability to monitor brain vascular ONOO(-) generation after injury with excellent temporal and spatial resolution. As a proof of concept, NP3 has enabled the direct visualization of neurovascular ONOO(-) formation in ischemia progression in live mouse brain by use of two-photon laser scanning microscopy. Due to these favorable properties, NP3 holds great promise for visualizing endogenous peroxynitrite fluxes in a variety of pathophysiological progressions in vitro and in vivo.
AuthorsXin Li, Rong-Rong Tao, Ling-Juan Hong, Juan Cheng, Quan Jiang, Ying-Mei Lu, Mei-Hua Liao, Wei-Feng Ye, Nan-Nan Lu, Feng Han, Yong-Zhou Hu, You-Hong Hu
JournalJournal of the American Chemical Society (J Am Chem Soc) Vol. 137 Issue 38 Pg. 12296-303 (Sep 30 2015) ISSN: 1520-5126 [Electronic] United States
PMID26352914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fluorescent Dyes
  • Peroxynitrous Acid
Topics
  • Animals
  • Cerebrovascular Trauma (metabolism, pathology)
  • Endothelial Cells (chemistry, metabolism)
  • Fluorescent Dyes (chemical synthesis, chemistry, pharmacokinetics)
  • Mice
  • Molecular Structure
  • Peroxynitrous Acid (chemistry, metabolism)

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