ArticleMetallomics : integrated biometal science2012
A systems approach implicates nuclear receptor targeting in the Atp7b(-/-) mouse model of Wilson's disease.
Article in Metallomics : integrated biometal science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- The gut-liver-kidney-brain axis in Wilson disease: copper speciation-flux and barrier-mediated organ crosstalk.Frontiers in immunology · 2026Review
- mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency.Journal of autoimmunity · 2023Article
- Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease.Pharmacology & therapeutics · 2023Review
- Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis.Nature metabolism · 2023Article
- ATP7B-Deficient Hepatocytes Reveal the Importance of Protein Misfolding Induced at Low Copper Concentration.Cells · 2022Article
- Oxysterol misbalance critically contributes to Wilson disease pathogenesis.Science advances · 2022Article
- Wilson Disease: Update on Pathophysiology and Treatment.Frontiers in cell and developmental biology · 2022Review
- Hepatic drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure.Pharmacological reports : PR · 2021Article
- Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease.Biomedicines · 2021Review
- Systemic deletion of Atp7b modifies the hepatocytes' response to copper overload in the mouse models of Wilson disease.Scientific reports · 2021Article
- Metabolic dysregulation in theProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes.International journal of molecular sciences · 2019Article
- Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- Altered zinc balance in the Atp7bMetallomics : integrated biometal science · 2018Article
- Animal models of Wilson disease.Journal of neurochemistry · 2018Review
- Host Cell Copper Transporters CTR1 and ATP7A are important for Influenza A virus replication.Virology journal · 2017Article
- Wilson Disease: Epigenetic effects of choline supplementation on phenotype and clinical course in a mouse model.Epigenetics · 2016Article
- The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria.The Journal of biological chemistry · 2016Article
- Modifying factors and phenotypic diversity in Wilson's disease.Annals of the New York Academy of Sciences · 2014Review
- The metabolomic window into hepatobiliary disease.Journal of hepatology · 2013Review
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Wilson's disease (WD) is an inherited disorder of copper metabolism characterized by liver disease and/or neurologic and psychiatric pathology. The disease is a result of mutation in ATP7B, which encodes the ATP7B copper transporting ATPase. Loss of copper transport function by ATP7B results in copper accumulation primarily in the liver, but also in other organs including the brain. Studies in the Atp7b(-/-) mouse model of WD revealed specific transcript and metabolic changes that precede development of liver pathology, most notably downregulation of transcripts in the cholesterol biosynthetic pathway. In order to gain insight into the molecular mechanisms of transcriptomic and metabolic changes, we used a systems approach analysing the pre-symptomatic hepatic nuclear proteome and liver metabolites. We found that ligand-activated nuclear receptors FXR/NR1H4 and GR/NR3C1 and nuclear receptor interacting partners are less abundant in Atp7b(-/-) hepatocyte nuclei, while DNA repair machinery and the nucleus-localized glutathione peroxidase, SelH, are more abundant. Analysis of metabolites revealed an increase in polyol sugar alcohols, indicating a change in osmotic potential that precedes hepatocyte swelling observed later in disease. This work is the first application of quantitative Multidimensional Protein Identification Technology (MuDPIT) to a model of WD to investigate protein-level mechanisms of WD pathology. The systems approach using "shotgun" proteomics and metabolomics in the context of previous transcriptomic data reveals molecular-level mechanisms of WD development and facilitates targeted analysis of hepatocellular copper toxicity.
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