Peptide-based inhibitors of the phagocyte NADPH oxidase.

Abstract

Phagocytes such as neutrophils, monocytes and macrophages play an essential role in host defenses against pathogens. To kill these pathogens, phagocytes produce and release large quantities of antimicrobial molecules such as reactive oxygen species (ROS), microbicidal peptides, and proteases. The enzyme responsible for ROS generation is called NADPH oxidase, or respiratory burst oxidase, and is composed of six proteins: gp91phox, p22phox, p47phox, p67phox, p40phox and Rac1/2. The vital importance of this enzyme in host defenses is illustrated by a genetic disorder called chronic granulomatous disease (CGD), in which the phagocyte NADPH oxidase is dysfunctional, leading to life-threatening recurrent bacterial and fungal infections. However, excessive NADPH oxidase activation and ROS over-production can damage surrounding tissues and participate in exaggerated inflammatory processes. As ROS production is believed to be involved in several inflammatory diseases, specific phagocyte NADPH oxidase inhibitors might have therapeutic value. In this commentary, we summarize the structure and activation of the phagocyte NADPH oxidase, and describe pharmacological inhibitors of this enzyme, with particular emphasis on peptide-based inhibitors derived from gp91phox, p22phox and p47phox.

• Authors: Jamel El-Benna, Pham My-Chan Dang, Axel Périanin
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 80 Issue 6 Pg. 778-85 (Sep 15 2010) ISSN: 1873-2968 [Electronic] England
• PMID: 20510204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Peptides
• NADPH Oxidases

Topics

• Amino Acid Sequence
• Animals
• Humans
• Molecular Sequence Data
• NADPH Oxidases (antagonists & inhibitors, chemistry, metabolism)
• Peptide Mapping (methods)
• Peptides (chemistry, metabolism)
• Phagocytes (drug effects, enzymology)