Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2

Gábor Csányi, Eugenia Cifuentes-Pagano, Imad Al Ghouleh, Daniel J. Ranayhossaini, Loreto Egaña, Lucia R. Lopes, Heather M. Jackson, Eric E. Kelley, Patrick J. Pagano

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

In recent years, reactive oxygen species (ROS) derived from the vascular isoforms of NADPH oxidase, Nox1, Nox2, and Nox4, have been implicated in many cardiovascular pathologies. As a result, the selective inhibition of these isoforms is an area of intense current investigation. In this study, we postulated that Nox2ds, a peptidic inhibitor that mimics a sequence in the cytosolic B-loop of Nox2, would inhibit ROS production by the Nox2-, but not the Nox1- and Nox4-oxidase systems. To test our hypothesis, the inhibitory activity of Nox2ds was assessed in cell-free assays using reconstituted systems expressing the Nox2-, canonical or hybrid Nox1-, or Nox4-oxidase. Our findings demonstrate that Nox2ds, but not its scrambled control, potently inhibited superoxide (O 2 •-) production in the Nox2 cell-free system, as assessed by the cytochrome c assay. Electron paramagnetic resonance confirmed that Nox2ds inhibits O 2 •- production by Nox2 oxidase. In contrast, Nox2ds did not inhibit ROS production by either Nox1- or Nox4-oxidase. These findings demonstrate that Nox2ds is a selective inhibitor of Nox2-oxidase and support its utility to elucidate the role of Nox2 in organ pathophysiology and its potential as a therapeutic agent.

Original languageEnglish (US)
Pages (from-to)1116-1125
Number of pages10
JournalFree Radical Biology and Medicine
Volume51
Issue number6
DOIs
StatePublished - Sep 15 2011

Keywords

  • Cardiovascular disease
  • Free radicals
  • NADPH oxidase
  • Nox inhibitor
  • Reactive oxygen species
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Csányi, G., Cifuentes-Pagano, E., Al Ghouleh, I., Ranayhossaini, D. J., Egaña, L., Lopes, L. R., Jackson, H. M., Kelley, E. E., & Pagano, P. J. (2011). Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2. Free Radical Biology and Medicine, 51(6), 1116-1125. https://doi.org/10.1016/j.freeradbiomed.2011.04.025