Mitigation of NADPH Oxidase 2 Activity as a Strategy to Inhibit Peroxynitrite Formation.

The Journal of Biological Chemistry
Jacek ZielonkaB Kalyanaraman

Abstract

Using high throughput screening-compatible assays for superoxide and hydrogen peroxide, we identified potential inhibitors of the NADPH oxidase (Nox2) isoform from a small library of bioactive compounds. By using multiple probes (hydroethidine, hydropropidine, Amplex Red, and coumarin boronate) with well defined redox chemistry that form highly diagnostic marker products upon reaction with superoxide (O2 (̇̄)), hydrogen peroxide (H2O2), and peroxynitrite (ONOO(-)), the number of false positives was greatly decreased. Selected hits for Nox2 were further screened for their ability to inhibit ONOO(-)formation in activated macrophages. A new diagnostic marker product for ONOO(-)is reported. We conclude that the newly developed high throughput screening/reactive oxygen species assays could also be used to identify potential inhibitors of ONOO(-)formed from Nox2-derived O2 (̇̄)and nitric oxide synthase-derived nitric oxide.

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Citations

Mar 29, 2020·The Journal of Biological Chemistry·Natalia RiosJacek Zielonka
Aug 2, 2016·British Journal of Pharmacology·G J McBeanF K Wallner
Jul 1, 2017·Cell Biochemistry and Biophysics·Jacek ZielonkaBalaraman Kalyanaraman
Apr 16, 2018·Journal of Leukocyte Biology·Zhen XuYan-Qing Ma
Oct 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Chenxia HeMarcelo G Bonini
May 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Rafael Radi
Apr 7, 2017·Interface Focus·Balaraman KalyanaramanMichael Dwinell
Oct 27, 2020·Frontiers in Chemistry·Adam SikoraBalaraman Kalyanaraman

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