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Review
. 2016:2016:3527579.
doi: 10.1155/2016/3527579. Epub 2015 Dec 28.

Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects (VSports在线直播)

Affiliations
Review

Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects

Maria Giulia Battelli (VSports) et al. Oxid Med Cell Longev. 2016.

Abstract

Xanthine oxidoreductase (XOR) is the enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is widely distributed among species. In addition to this housekeeping function, mammalian XOR is a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various pathways. This review intends to address the physiological and pathological roles of XOR-derived oxidant molecules VSports手机版. The cytocidal action of XOR products has been claimed in relation to tissue damage, in particular damage induced by hypoxia and ischemia. Attempts to exploit this activity to eliminate unwanted cells via the construction of conjugates have also been reported. Moreover, different aspects of XOR activity related to phlogosis, endothelial activation, leukocyte activation, and vascular tone regulation, have been taken into consideration. Finally, the positive and negative outcomes concerning cancer pathology have been analyzed because XOR products may induce mutagenesis, cell proliferation, and tumor progression, but they are also associated with apoptosis and cell differentiation. In conclusion, XOR activity generates free radicals and other oxidant reactive species that may result in either harmful or beneficial outcomes. .

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Figures

Figure 1
Figure 1
Pharmaceutical applications of xanthine oxidoreductase (XOR) cytotoxicity. (a) Mechanisms of ROS cytotoxicity: ROS induce peroxidation of membrane lipids, DNA damage, and protein oxidation and lead to cell death, mainly via apoptosis through impaired mitochondrial function (reviewed in [13]). (b) XOR was conjugated to carriers for the experimental elimination of specific target cells. Selective cell killing was obtained by conjugating XOR to an antibody that was able to specifically deliver reactive oxygen species (ROS) to target cells [23]. Enhanced ROS delivery to solid tumors was achieved by XOR conjugation to polyethylene glycol (PEG) [24].
Figure 2
Figure 2
Prophlogistic action of reactive oxygen (ROS) and nitrogen (RNS) species. (a) Interferon and other cytokines increase xanthine oxidoreductase gene (XOR) expression as well as the conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) and XOR serum level (reviewed in [11]). XOR-derived ROS and RNS mediate the endothelial and phagocytic cell activation that is functional in antibacterial defense (reviewed in [30]). (b) XOR products induce endothelial permeabilization and dysregulation of vascular tone, which may lead to thrombosis and atherosclerosis (reviewed in [37]).
Figure 3
Figure 3
Cancer pathogenesis: ambiguous role of xanthine oxidoreductase (XOR). XOR-derived ROS may activate genes responsible for each phase of cancer development (reviewed in [47]) as well as genes that promote antioncogenic activities (reviewed in [45]).

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