Xanthine oxidoreductase-catalyzed reactive species generation: A process in critical need of reevaluation

Nearly 30 years have passed since the discovery of xanthine oxidoreductase (XOR) as a critical source of reactive species in ischemia/reperfusion injury. Since then, numerous inflammatory disease processes have been associated with elevated XOR activity and allied reactive species formation solidify...

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Bibliographic Details
Published inRedox biology Vol. 1; no. 1; pp. 353 - 358
Main Authors Cantu-Medellin, Nadiezhda, Kelley, Eric E
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier 01.01.2013
Subjects
Animals
Biocatalysis
Free radicals
Free Radicals - metabolism
Graphical Review
Humans
Hypoxia
Inflammation
Nitric oxide
Nitric Oxide - metabolism
Nitrite
Oxygen tension
Reactive Oxygen Species - metabolism
Xanthine Dehydrogenase - metabolism
Xanthine oxidoreductase
Free radicals
I/R, ischemia/reperfusion
XDH, xanthine dehydrogenase
H2O2, hydrogen peroxide
Inflammation
NOS, nitric oxide synthase
Nitrite
XO, xanthine oxidase
XOR, xanthine oxidoreductase
NO, nitric oxide
Nitric oxide
Xanthine oxidoreductase
Hypoxia
GAGs, glycosaminoglycans
ROS, reactive oxygen species
Oxygen tension
O2•−, superoxide
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Summary:Nearly 30 years have passed since the discovery of xanthine oxidoreductase (XOR) as a critical source of reactive species in ischemia/reperfusion injury. Since then, numerous inflammatory disease processes have been associated with elevated XOR activity and allied reactive species formation solidifying the ideology that enhancement of XOR activity equates to negative clinical outcomes. However, recent evidence may shatter this paradigm by describing a nitrate/nitrite reductase capacity for XOR whereby XOR may be considered a crucial source of beneficial (•)NO under ischemic/hypoxic/acidic conditions; settings similar to those that limit the functional capacity of nitric oxide synthase. Herein, we review XOR-catalyzed reactive species generation and identify key microenvironmental factors whose interplay impacts the identity of the reactive species (oxidants vs. (•)NO) produced. In doing so, we redefine existing dogma and shed new light on an enzyme that has weathered the evolutionary process not as gadfly but a crucial component in the maintenance of homeostasis.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
ISSN:2213-2317
2213-2317
DOI:10.1016/j.redox.2013.05.002