ArticlePloS one2012
Untargeted plasma metabolite profiling reveals the broad systemic consequences of xanthine oxidoreductase inactivation in mice.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Trial
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- Maternal postpartum sedentary life exacerbates the metabolic impact of moderately fat-rich diet in male mice.npj metabolic health and disease · 2025Article
- Potential Opportunities for Pharmacogenetic-Based Therapeutic Exploitation of Xanthine Dehydrogenase in Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Measurement of Melanin Metabolism in Live Cells by [U-The Journal of investigative dermatology · 2021Article
- Genetic analysis of Pycr1 and Pycr2 in mice.Genetics · 2021Article
- Accelerated transsulfuration metabolically defines a discrete subclass of amyotrophic lateral sclerosis patients.Neurobiology of disease · 2020Article
- APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice.Scientific reports · 2020Article
- Combined Metabolomics and Genome-Wide Transcriptomics Analyses Show Multiple HIF1α-Induced Changes in Lipid Metabolism in Early Stage Clear Cell Renal Cell Carcinoma.Translational oncology · 2020Article
- Febuxostat, a Xanthine Oxidoreductase Inhibitor, Decreases NLRP3-dependent Inflammation in Macrophages by Activating the Purine Salvage Pathway and Restoring Cellular Bioenergetics.Scientific reports · 2019Article
- FTO controls reversible mNature chemical biology · 2019Article
- Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease).Scientific reports · 2018Article
- Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations.Cell metabolism · 2018Article
- Partitioning of One-Carbon Units in Folate and Methionine Metabolism Is Essential for Neural Tube Closure.Cell reports · 2017Article
- Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer's disease-like pathology.Nature communications · 2017Article
- Multi-omics analysis reveals that ornithine decarboxylase contributes to erlotinib resistance in pancreatic cancer cells.Oncotarget · 2017Article
- Overexpression and Suppression ofFrontiers in plant science · 2017Article
- Metabolomic network analysis of estrogen-stimulated MCF-7 cells: a comparison of overrepresentation analysis, quantitative enrichment analysis and pathway analysis versus metabolite network analysis.Archives of toxicology · 2017Article
- Behavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms.Nature communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
A major challenge in systems biology is integration of molecular findings for individual enzyme activities into a cohesive high-level understanding of cellular metabolism and physiology/pathophysiology. However, meaningful prediction for how a perturbed enzyme activity will globally impact metabolism in a cell, tissue or intact organisms is precluded by multiple unknowns, including in vivo enzymatic rates, subcellular distribution and pathway interactions. To address this challenge, metabolomics offers the potential to simultaneously survey changes in thousands of structurally diverse metabolites within complex biological matrices. The present study assessed the capability of untargeted plasma metabolite profiling to discover systemic changes arising from inactivation of xanthine oxidoreductase (XOR), an enzyme that catalyzes the final steps in purine degradation. Using LC-MS coupled with a multivariate statistical data analysis platform, we confidently surveyed >3,700 plasma metabolites (50-1,000 Da) for differential expression in XOR wildtype vs. mice with inactivated XOR, arising from gene deletion or pharmacological inhibition. Results confirmed the predicted derangements in purine metabolism, but also revealed unanticipated perturbations in metabolism of pyrimidines, nicotinamides, tryptophan, phospholipids, Krebs and urea cycles, and revealed kidney dysfunction biomarkers. Histochemical studies confirmed and characterized kidney failure in xor-nullizygous mice. These findings provide new insight into XOR functions and demonstrate the power of untargeted metabolite profiling for systemic discovery of direct and indirect consequences of gene mutations and drug treatments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.