Xanthine Oxidoreductase Gene Expression and Enzyme Activity in Developing Human Tissues

Saksela, Mika; Lapatto, Risto; Raivio, Kari O.

doi:10.1159/000014034

Cited by 47 publications

(26 citation statements)

References 30 publications

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“…XOR activity was calculated by using [ 14 C]xanthine as substrate and separating the product uric acid by high-performance liquid chromatography as described (20).…”

Section: Methodsmentioning

confidence: 99%

Down-Regulated Xanthine Oxidoreductase Is a Feature of Aggressive Breast Cancer

Linder

Lundin

Isola

et al. 2005

Clinical Cancer Research

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Purpose: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA, and high-energy phosphates and also plays a role in milk lipid globule secretion. Given the strong and regulated expression of XOR in normal breast epithelium, and the previously shown alterations of its expression in experimental tumorigenesis, we hypothesized that XOR may be differentially expressed in breast cancer. Experimental Design: XOR expression was analyzed by immunohistochemistry in tissue microarray specimens of 1,262 breast cancer patients with a median follow-up of 9.5 years. Results: Expression of XOR was moderately decreased in 50% and undetectable in another 7% of the tumors. Decreased XOR expression was associated with poor histologic grade of differentiation, ductal and lobular histologic types, large tumor size, high number of positive axillary lymph nodes, and high cyclooxygenase-2 expression, but not with estrogen or progesterone receptor status, Ki-67, p53, or ERBB2 amplification. Absence of XOR expression was associated with unfavorable outcome, and patients with no XOR expression had more than twice the risk of distant recurrence as compared with those with a moderately decreased or normal expression (hazard ratio, 2.21; P < 0.0001). This was also true in patients with node-negative disease (hazard ratio, 2.75; P < 0.0001) as well as in patients with small (V1cm) tumors (hazard ratio, 3.09; P = 0.027). In a multivariate survival analysis, negative XOR emerged as an independent prognostic factor both in the entire series (P = 0.01) and among patients with nodenegative disease (P = 0.0009). Conclusion: Loss of XOR identifies breast cancer patients with unfavorable prognosis.

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“…XOR activity was calculated by using [ 14 C]xanthine as substrate and separating the product uric acid by high-performance liquid chromatography as described (20).…”

Section: Methodsmentioning

confidence: 99%

Down-Regulated Xanthine Oxidoreductase Is a Feature of Aggressive Breast Cancer

Linder

Lundin

Isola

et al. 2005

Clinical Cancer Research

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“…XOR activity was measured by using [ 14 C]xanthine (0.1 mM, specific activity 58 mCi/mmol) (NEN; Life Science Products, Boston, MA) as substrate and separating the product uric acid by HPLC as described (31). For total XOR activity (XDH ϩ XO), NAD ϩ (400 M) was present, whereas for XO assay, NAD ϩ was omitted.…”

Section: Methodsmentioning

confidence: 99%

Posttranslational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions

Linder

Martelin

Lapatto

et al. 2003

American Journal of Physiology-Cell Physiology

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O. Raivio. Posttranslational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions. Am J Physiol Cell Physiol 285: C48-C55, 2003. First published March 12, 2003 10.1152/ajpcell.00561.2002 catalyzes the final reactions of purine catabolism and may account for cell damage by producing reactive oxygen metabolites in cells reoxygenated after hypoxia. We found a three-to eightfold higher XOR activity in cultured human bronchial epithelial cells exposed to hypoxia (0.5-3% O 2) compared with cells grown in normoxia (21% O 2) but no difference in XOR protein or mRNA. XOR promoter constructs failed to respond to hypoxia. The cellular XOR activity at 3% O 2 returned to basal levels when the cells were returned to 21% O 2, and hyperoxia (95% O2) abolished enzyme activity with no change in XOR protein.Our data suggest reversible enzyme inactivation by oxygen or its metabolites. NADH was normally oxidized by the oxygen-inactivated enzyme, which rules out damage to the flavin adenine dinucleotide cofactor. Hydrogen peroxide partially inactivated the molybdenum center of XOR, as shown by a parallel decrease in XOR-catalyzed xanthine oxidation and dichlorophenolindophenol reduction. We conclude that the transcription or translation of XOR is not influenced by hypoxia or hyperoxia. Instead, the molybdenum center of XOR is posttranslationally inactivated by oxygen metabolites in "normal" (21% O 2) cell culture atmosphere. This inactivation is reversed in hypoxia and accounts for the apparent induction. xanthine oxidase; hypoxia; hyperoxia; ischemia reperfusion

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“…Human homologs of rosy/XDH and white (ABCG1) have been cloned and mapped, and both are expressed in several tissues including the brain (Ichida et al 1993;Xu et al 1994;Chen et al 1996;Croop et al 1997;Saksela et al 1998). Mutations in ABCG1 are associated with mood and panic disorders (Nakamura et al 1999), and mutations in white and brown have a range of neurobehavioral effects in flies, including reduced sensitivity to anesthesia, learning defects, and abnormal courtship behavior (Zhang and Odenwald 1995;Campbell and Nash 2001;Diegelmann et al 2006).…”

Section: /Wmentioning

confidence: 99%

Interaction Between Eye Pigment Genes and Tau-Induced Neurodegeneration inDrosophila melanogaster

Ambegaokar

Jackson

2010

Genetics

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Null mutations in the genes white and brown, but not scarlet, enhance a rough eye phenotype in a Drosophila melanogaster model of tauopathy; however, adding rosy mutations suppresses these effects. Interaction with nucleotide-derived pigments or increased lysosomal dysregulation are potential mechanisms. Finally, tau toxicity correlates with increased GSK-3b activity, but not with tau phosphorylation at Ser202/Thr205.

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Xanthine Oxidoreductase Gene Expression and Enzyme Activity in Developing Human Tissues

Cited by 47 publications

References 30 publications

Down-Regulated Xanthine Oxidoreductase Is a Feature of Aggressive Breast Cancer

Down-Regulated Xanthine Oxidoreductase Is a Feature of Aggressive Breast Cancer

Posttranslational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions

Interaction Between Eye Pigment Genes and Tau-Induced Neurodegeneration inDrosophila melanogaster

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