Disease relevance of Uox

• Hyperuricemia and urate nephropathy in urate oxidase-deficient mice [1].
• All five mice injected with transformed A-U3 cells developed adenocarcinomas, but no tumors developed in mice injected with control CV-1 cells or cells stably expressing UOX that were not exposed to uric acid [2].
• Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase [3].

High impact information on Uox

• Urate oxidase, or uricase (EC 1.7.3.3), is a purine metabolic enzyme that catalyzes the conversion of uric acid to allantoin in most mammals except humans and certain other primates [1].
• Five stably transfected CV-1 cell lines expressing recombinant rat UOX were isolated in which the recombinant protein was targeted to peroxisomes and formed crystalloid structures or cores similar to those present in rat liver peroxisomes [2].
• Transformation of epithelial cells stably transfected with H2O2-generating peroxisomal urate oxidase [2].
• The three-dimensional imaging technique was applied to uricase knockout mice to demonstrate the method for the evaluation of morphologic phenotype [4].
• Neither of the two cell lines contained any appreciable urate oxidase activity [5].

Chemical compound and disease context of Uox

• Oxonic acid effectively, though transiently, blocked the uricase activity in both dydy and Dydy mice resulting in hyperuricemia and hyperuricosuria with decreased allantoin [6].

Biological context of Uox

• The mouse urate oxidase gene, Uox, maps to distal chromosome 3 [7].
• Southern blot analyses of urate oxidase, Uox, show two RFLPs of genomic mutant DNA: an EcoRI site between exons 4-8 and a BamHI site 3' to exon 6 [8].
• Tissue distribution of the 111In-labeled UC in these conjugates was evaluated by a tissue uptake clearance index calculated in terms of clearance [9].
• Through phylogenetic genome comparison, we identify here two genes that share with urate oxidase a common history of loss or gain events [10].
• Here we provide evidence that mouse transthyretin-related protein facilitates the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction [11].

Anatomical context of Uox

• To create a mouse model for hyperuricemia and gout, and to address the question of whether urate oxidase is essential in lower mammalian species, we have disrupted the urate oxidase gene in the mouse by homologous recombination in embryonic stem cells [1].
• Distribution of TSO-hydrolase activity in the sucrose density gradient fractions closely resembled the activity distribution of the peroxisomal markers catalase and urate oxidase, but significant activity was also found in mitochondria [12].
• Urate oxidase was mostly recovered in a 40 000 g for 20 min subcellular fraction from conventional homogenated [13].
• Using mouse small intestine brush-border membrane vesicles virtually free of xanthine oxidase (EC 1.2.3.2) and free of uricase (EC 1.7.3.3) the uptake of the purines uric acid, xanthine and hypoxanthine have been studied [14].

Associations of Uox with chemical compounds

• At day 300 the clofibrate treatment increased all activities although UOX was not significantly increased [15].
• Urate oxidase, or uricase (EC 1.7.3.3), is a peroxisomal enzyme that catalyzes the oxidation of uric acid to allantoin in most mammals [16].
• Acyl-CoA oxidase, catalase and uricase activities were increased by 712%, 506% and 41% respectively by treatment with fenofibrate [17].
• (6) The linear poly(ethylene glycol) conjugate was, among the various uricase forms, the species with the lowest distribution levels in all the examined organs [18].
• The activity of catalase in the mitochondrial fraction from female mice was not affected by vitamin A deficiency, whereas the activity of peroxisomal urate oxidase was increased 2.9-fold [19].

Other interactions of Uox

• In control mice, UOX activity was not affected by aging whereas CAT and AOX activities were significantly decreased [15].
• In contrast, protein levels of two PPARalpha-unresponsive peroxisomal enzymes, catalase and urate oxidase, were not affected by the loss of STAT5b [20].
• In the liver of mice fed this diet for 3 wk, hepatic catalase activity was increased to 140% while no induction of palmitoyl-CoA oxidase (EC 1.3.99.3), urate oxidase (EC 1.7.3.3), and L-alpha-hydroxyisovalerate oxidase (EC 1.1.3.a) was observed [21].
• Induction of tolerance in mice by uricase and monomethoxypolyethylene glycol-modified uricase [22].

Analytical, diagnostic and therapeutic context of Uox

• In Group I, 1.6 mg allopurinol and 0.2 mg of uricase were injected i.p. for 3 days prior to cell transplantation [23].
• CONCLUSIONS: Allopurinol/uricase and ibuprofen enhance differentiated hESC-engraftment and myocardial restoration following transplantation into the injured heart [23].
• Following a single intraperitoneal injection of oxonic acid, urate-oxidase inhibitor with optical and chromatographic properties of the injected drug was found in the supernatants of mouse liver homogenates [24].

References