Xanthine oxidoreductase-catalyzed reactive species generation: A process in critical need of reevaluation.
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TLDR
XOR-catalyzed reactive species generation is reviewed and key microenvironmental factors whose interplay impacts the identity of the reactive species (oxidants vs. •NO) produced are identified.Abstract:
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.read more
Citations
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Current Mechanistic Concepts in Ischemia and Reperfusion Injury.
Meng-Yu Wu,Giou Teng Yiang,Wan Ting Liao,Andy Po-Yi Tsai,Yeung-Leung Cheng,Pei Wen Cheng,Chia Ying Li,Chia-Jung Li +7 more
TL;DR: This review article presents recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways and highlights the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes.
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Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine
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