title: Xanthine Oxidoreductase-Derived Reactive Species: Physiological and Pathological Effects.
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. 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.
authors.affiliation: Alma Mater Studiorum-University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Unit, Via S. Giacomo 14, 40126 Bologna, Italy.
authors.forename: Maria Giulia
authors.identifier: 0000-0001-6048-0454
authors.initials: MG
authors.lastname: Battelli
authors.affiliation: Alma Mater Studiorum-University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Unit, Via S. Giacomo 14, 40126 Bologna, Italy.
authors.forename: Letizia
authors.identifier: 0000-0001-8051-4981
authors.initials: L
authors.lastname: Polito
authors.affiliation: Alma Mater Studiorum-University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Unit, Via S. Giacomo 14, 40126 Bologna, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bortolotti
authors.affiliation: Alma Mater Studiorum-University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), General Pathology Unit, Via S. Giacomo 14, 40126 Bologna, Italy.
authors.forename: Andrea
authors.identifier: 0000-0001-7497-4586
authors.initials: A
authors.lastname: Bolognesi
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D017209:Apoptosis; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000737:chemistry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014638:Vanadates / Q000737:chemistry; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005609:Free Radicals; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D014638:Vanadates; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases
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