期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 51, 期 6, 页码 1116-1125出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.04.025
关键词
NADPH oxidase; Reactive oxygen species; Superoxide; Nox inhibitor; Cardiovascular disease; Free radicals
资金
- National Institutes of Health [HL079207, HL55425]
- Vascular Medicine Institute
- Institute for Transfusion Medicine
- Hemophilia Center of Western Pennsylvania
- American Heart Association
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 Noxl- 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(center dot-)) production in the Nox2 cell-free system, as assessed by the cytochrome c assay. Electron paramagnetic resonance confirmed that Nox2ds inhibits O-2(center dot-) 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. (C) 2011 Elsevier Inc. All rights reserved.
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