Oxidases and oxygenases in regulation of vascular nitric oxide signaling and inflammatory responses.
Nitric oxide (.NO) is a freely diffusible inter- and intracellular messenger produced by a variety of mammalian cells including vascular endothelium, neurons, smooth muscle cells, macrophages, neutrophils, platelets, and pulmonary epithelium. In smooth muscle cells, platelets, and neutrophils, .NO raises intracellular cyclic guanasine 5'-monophosphate levels by reacting with the catalytic heme domain of guanylate cylase, to activate it, thus leading to vasorelaxation, inhibition of platelet aggregation and inhibition of platelet and inflammatory cell adhesion to endothelium. The physiologic actions of .NO are highly dependent on changes in steady-state concentrations of reactive species and tissue-oxidant defense mechanisms. Vessel wall oxidases and oxygenases, in particular, are critical sources of oxygen radical production and can lead to an overall impairment of vascular .NO signaling, via the metalloprotein and free radical-mediated consumption of this vasoactive molecule. Vascular oxidase and oxygenase activities can thus account for the functional inactivation of .NO, leading to a prooxidative milieu and chronic inflammation.
Aslan
Mutay
M
Department of Anesthesiology, The Center for Free Radical Biology, University of Alabama at Birmingham, 35233, USA.
Freeman
Bruce A
BA
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014969:Xanthine Oxidase / Q000378:metabolism
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D009195:Peroxidase; D010105:Oxygenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D014969:Xanthine Oxidase