A new paradigm for XOR-catalyzed reactive species generation in the endothelium

Pharmacological Reports : PR
Eric E Kelley

Abstract

A plethora of vascular pathology is associated with inflammation, hypoxia and elevated rates of reactive species generation. A critical source of these reactive species is the purine catabolizing enzyme xanthine oxidoreductase (XOR) as numerous reports over the past 30 years have demonstrated XOR inhibition to be salutary. Despite this long standing association between increased vascular XOR activity and negative clinical outcomes, recent reports reveal a new paradigm whereby the enzymatic activity of XOR mediates beneficial outcomes by catalyzing the one electron reduction of nitrite (NO2(-)) to nitric oxide (NO) when NO2(-) and/or nitrate (NO3(-)) levels are enhanced either via dietary or pharmacologic means. These observations seemingly countervail numerous reports of improved outcomes in similar models upon XOR inhibition in the absence of NO2(-) treatment affirming the need for a more clear understanding of the mechanisms underpinning the product identity of XOR. To establish the micro-environmental conditions requisite for in vivo XOR-catalyzed oxidant and NO production, this review assesses the impact of pH, O2 tension, enzyme-endothelial interactions, substrate concentrations and catalytic differences between xanthine o...Continue Reading

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Citations

Sep 1, 2015·Pharmacological Reports : PR·Stefan Chlopicki
Oct 23, 2016·Free Radical Biology & Medicine·Maria PeleliMattias Carlström
Nov 15, 2017·Antioxidants·Denise BurtenshawPaul A Cahill
Apr 13, 2018·Circulation Journal : Official Journal of the Japanese Circulation Society·Masato FuruhashiTetsuji Miura
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Dec 6, 2018·Journal of Diabetes Investigation·Masato FuruhashiTetsuji Miura
Aug 17, 2018·Current Drug Targets·Gustavo H Oliveira-Paula, Jose E Tanus-Santos
Feb 12, 2020·The Journal of International Medical Research·Yang YangLizheng Qin
Sep 8, 2020·American Journal of Physiology. Endocrinology and Metabolism·Masato Furuhashi
Aug 21, 2019·Frontiers in Cardiovascular Medicine·Denise BurtenshawPaul A Cahill
Sep 28, 2017·Current Medical Research and Opinion·Claudio Borghi
Mar 7, 2019·Frontiers in Pharmacology·Todd A JohnsonNaoyuki Kamatani
Jun 14, 2019·Dose-response : a Publication of International Hormesis Society·Hoon JungDong Gun Lim
Jan 5, 2019·Doklady. Biochemistry and Biophysics·A S GorbunovaB N Ivanov
Sep 28, 2017·Current Medical Research and Opinion·Carmine Zoccali
Oct 18, 2020·International Journal of Molecular Sciences·Pamela PignatelliMaria Cristina Curia
Nov 20, 2020·Journal of Diabetes Investigation·Yusuke KawachiIichiro Shimomura
Mar 7, 2021·International Journal of Environmental Research and Public Health·Yuka KotozakiMakoto Sasaki
Jan 14, 2021·Transplantation Direct·Tara TalaieChristine L Lau
Jun 13, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masato FuruhashiTetsuji Miura
Feb 5, 2019·Nitric Oxide : Biology and Chemistry·Gustavo H Oliveira-PaulaJose E Tanus-Santos

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