The NADPH oxidase family and its inhibitors.
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.
Department of Cardiovascular Physiology, Experimental and Clinical Physiology, Medical University of Łódź, Poland. kleniewska.p@interia.pl
Paulina
P
Kleniewska
Aleksandra
A
Piechota
Beata
B
Skibska
Anna
A
Gorąca
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases