Towards specific NADPH oxidase inhibition by small synthetic peptides.

Abstract

Reactive oxygen species (ROS) production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. ROS are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Excessive NADPH oxidase activation and ROS overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation. NADPH oxidase is a complex enzyme composed of six proteins: gp91phox (renamed NOX2), p22phox, p47phox, p67phox, p40phox and Rac1/2. Inhibitors of this enzyme could be beneficial, by limiting ROS production and inappropriate inflammation. A few small non-peptide inhibitors of NADPH oxidase are currently used to inhibit ROS production, but they lack specificity as they inhibit NADPH oxidase homologues or other unrelated enzymes. Peptide inhibitors that target a specific sequence of NADPH oxidase components could be more specific than small molecules. Here we review peptide-based inhibitors, with particular focus on a molecule derived from gp91phox/NOX2 and p47phox, and discuss their possible use as specific phagocyte NADPH oxidase inhibitors.

• Authors: Jamel El-Benna, Pham My-Chan Dang, Axel Périanin
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 69 Issue 14 Pg. 2307-14 (Jul 2012) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 22562604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Enzyme Inhibitors
• Membrane Glycoproteins
• Peptides
• Reactive Oxygen Species
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Animals
• Enzyme Inhibitors (chemistry, metabolism)
• Humans
• Membrane Glycoproteins (antagonists & inhibitors, metabolism)
• NADPH Oxidase 2
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Neutrophils (metabolism)
• Peptides (chemistry, metabolism)
• Phagocytes (enzymology, metabolism)
• Reactive Oxygen Species (metabolism)