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The NADPH Oxidase Family and its Inhibitors

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  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The classical nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was originally detected in neutrophils as a multicomponent enzyme that catalyzes the generation of superoxide from oxygen and the reduced form of NADPH. This enzyme is composed of two membrane-bound subunits (p22phox and gp91phox), three cytosolic subunits (p67phox, p47phox, and p40phox) and a small G-protein Rac (Rac1 and Rac2). Recently, it has been demonstrated that there are several isoforms of nonphagocytic NADPH oxidase. Endothelial cells, vascular smooth muscle cells or adventitial fibroblasts possess multiple isoforms of this enzyme. The new homologs, along with gp91phox are now designated the Nox family of NADPH oxidases and are key sources of reactive oxygen species in the vasculature. Reactive oxygen species play a significant role in regulating endothelial function and vascular tone. However, besides the participation in the processes of physiological cell, these enzymes can also be the perpetrator of oxidative stress that causes endothelial dysfunction. This review summarizes the current state of knowledge of the structure and functions of NADPH oxidase and NADPH oxidase inhibitors in the treatment of disorders with endothelial damage.

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Abbreviations

ROS:

Reactive oxygen species

PKC:

Protein kinase C

H2O2 :

Hydrogen peroxide

GSH:

Reduced glutathione

NO:

Nitric oxide

MPO:

Myeloperoxidase

DPI:

Diphenyleneiodonium chloride

AEBSF:

4-(2-aminoethyl)-benzenesulphonyl fluoride; S17834: 1,4-dimethyl-2,3,5,6-tetraiodobenzene

VAS-2870:

3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5- d) pyrimidine

PR-39:

Proline-arginine-rich antimicrobial peptide

VEGF:

Vascular endothelial growth factor

TNF-α:

Tumor necrosis factor α

ox-LDL:

Oxidized low-density lipoprotein

AGEs:

Advanced glycation end-products

NEFAs:

Non-esterified fatty acids

PDGF:

Platelet-derived growth factor

VSMCs:

Vascular smooth muscles cells

FAD:

Flavin adenine dinucleotide

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Acknowledgments

The study was supported by a grant 503/0-079-03/503-01 and 503/3-021-01/503-01 from the Medical University of Łódź.

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  1. Department of Cardiovascular Physiology, Experimental and Clinical Physiology, Medical University of Łódź, Mazowiecka 6/8, 92-215, Łódź, Poland

    Paulina Kleniewska, Aleksandra Piechota & Anna Gorąca

  2. Department of Applied Pharmacy, Department of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151, Łódź, Poland

    Beata Skibska

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  1. Paulina Kleniewska
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Correspondence to Paulina Kleniewska.

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Kleniewska, P., Piechota, A., Skibska, B. et al. The NADPH Oxidase Family and its Inhibitors. Arch. Immunol. Ther. Exp. 60, 277–294 (2012). https://doi.org/10.1007/s00005-012-0176-z

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