ArticleHepatology (Baltimore, Md.)2013
Wilson's disease: changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 108 citations in OpenAlex.
- [Development and validation of a machine learning-based prediction model for fatty liver in Wilson disease].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026Article
- Biological Effects of D-Penicillamine on Copper Sulfate-Induced Possible Damage in the Caudate Nucleus: Role of Apoptotic Genes Bax, Bcl2, and Bax-Bcl2 Ratio.Biological trace element research · 2026Article
- High copper levels induce oxidative stress and inflammatory processes in a cell culture model of Wilson's disease.Molecular and cellular biochemistry · 2026Article
- Copper homeostasis and pregnancy complications: a comprehensive review.Journal of assisted reproduction and genetics · 2025Review
- Comparative review of copper-associated chronic hepatitis in dogs and Wilson disease in humans.Frontiers in veterinary science · 2025Review
- Chinese Multidisciplinary Expert Consensus on Orphan/Anticopper Drugs and Other Non-drug Management of Hepatolenticular Degeneration.Current neuropharmacology · 2025Review
- Article
- Wilson's Disease-Crossroads of Genetics, Inflammation and Immunity/Autoimmunity: Clinical and Molecular Issues.International journal of molecular sciences · 2024Review
- A case of Wilson's disease combined with intracranial lipoma and dysplasia of the corpus callosum with review of the literature.BMC neurology · 2024Review
- Transcriptomic evaluation of N6-methyladenosine modification can be used to identify differentially gene and immune-related biological processes in TX mice with liver fibrosis.Molecular biology reports · 2024Article
- Late-onset Wilson Disease in a Patient Followed-up for Nonalcoholic Fatty Liver Disease.Internal medicine (Tokyo, Japan) · 2024Article
- The Tao of Copper Metabolism: From Physiology to Pathology.Current medicinal chemistry · 2024Review
- Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024Review
- Effects of Copper or Zinc Organometallics on Cytotoxicity, DNA Damage and Epigenetic Changes in the HC-04 Human Liver Cell Line.International journal of molecular sciences · 2023Article
- [Factors influencing the clinical phenotype of hepatolenticular degeneration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Review
- Methyl Group Metabolism in Differentiation, Aging, and Cancer.International journal of molecular sciences · 2022Review
- Review
- Wilson Disease: Update on Pathophysiology and Treatment.Frontiers in cell and developmental biology · 2022Review
- The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledHepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson's disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b), and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum alanine aminotransferase (ALT) and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels.
conclusionReduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD.
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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.