Molecular imaging of peroxynitrite with HKGreen-4 in live cells and tissues

J Am Chem Soc. 2014 Aug 20;136(33):11728-34. doi: 10.1021/ja504624q. Epub 2014 Aug 7.

Abstract

Peroxynitrite (ONOO(-)), the product of a radical combination reaction of nitric oxide and superoxide, is a potent biological oxidant involved in a broad spectrum of physiological and pathological processes. Herein we report the development, characterization, and biological applications of a new fluorescent probe, HKGreen-4, for peroxynitrite detection and imaging. HKGreen-4 utilizes a peroxynitrite-triggered oxidative N-dearylation reaction to achieve an exceptionally sensitive and selective fluorescence turn-on response toward peroxynitrite in chemical systems and biological samples. We have thoroughly evaluated the utility of HKGreen-4 for intracellular peroxynitrite imaging and, more importantly, demonstrated that HKGreen-4 can be efficiently employed to visualize endogenous peroxynitrite generated in Escherichia coli-challenged macrophages and in live tissues from a mouse model of atherosclerosis. This probe should serve as a powerful molecular imaging tool to explore peroxynitrite biology under a variety of physiological and pathological contexts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Atherosclerosis / pathology*
  • Cell Line
  • Cell Survival
  • Disease Models, Animal
  • Fluorescent Dyes / chemistry*
  • Heart
  • Macrophages / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Imaging*
  • Molecular Structure
  • Peroxynitrous Acid / chemistry*
  • Rhodamines / chemistry*

Substances

  • Apolipoproteins E
  • Fluorescent Dyes
  • HKGreen-4
  • Rhodamines
  • Peroxynitrous Acid