ArticleThe Journal of biological chemistry2010
Nickel ions inhibit histone demethylase JMJD1A and DNA repair enzyme ABH2 by replacing the ferrous iron in the catalytic centers.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 143 citations in OpenAlex.
- Atmospheric Particulate Matter as a Carrier of Pb, Cd, and Ni: From Environmental Transfer and Bioaccessibility to Molecular Toxicity and Predictive Modeling.Journal of xenobiotics · 2026Review
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- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Fine particulate matter‑induced cardiac developmental toxicity (Review).Experimental and therapeutic medicine · 2025Review
- Air pollution and pregnancy.Seminars in perinatology · 2023Article
- Profiling Metal-Induced Genotoxic Endpoints.Journal of environmental health · 2023Article
- Advances in bioleaching of waste lithium batteries under metal ion stress.Bioresources and bioprocessing · 2023Review
- Review
- Conformational Dynamics of Human ALKBH2 Dioxygenase in the Course of DNA Repair as Revealed by Stopped-Flow Fluorescence Spectroscopy.Molecules (Basel, Switzerland) · 2022Article
- Epigenetic mechanisms in metal carcinogenesis.Toxicology reports · 2022Review
- Epithelial-mesenchymal transition: Insights into nickel-induced lung diseases.Seminars in cancer biology · 2021Review
- Immunological Mechanisms of Metal Allergies and the Nickel-Specific TCR-pMHC Interface.International journal of environmental research and public health · 2021Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer.Molecular cancer research : MCR · 2021Review
- Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre crystal-chemical and physical parameters to the key characteristics of cancer.Current research in toxicology · 2021Article
- Environmental influence on neurodevelopmental disorders: Potential association of heavy metal exposure and autism.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2020Review
- From air pollution to cardiovascular diseases: the emerging role of epigenetics.Molecular biology reports · 2020Review
- Aspartate/asparagine-β-hydroxylase: a high-throughput mass spectrometric assay for discovery of small molecule inhibitors.Scientific reports · 2020Article
- Nickel: Human Health and Environmental Toxicology.International journal of environmental research and public health · 2020Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Iron- and 2-oxoglutarate-dependent dioxygenases are a diverse family of non-heme iron enzymes that catalyze various important oxidations in cells. A key structural motif of these dioxygenases is a facial triad of 2-histidines-1-carboxylate that coordinates the Fe(II) at the catalytic site. Using histone demethylase JMJD1A and DNA repair enzyme ABH2 as examples, we show that this family of dioxygenases is highly sensitive to inhibition by carcinogenic nickel ions. We find that, with iron, the 50% inhibitory concentrations of nickel (IC(50) [Ni(II)]) are 25 microm for JMJD1A and 7.5 microm for ABH2. Without iron, JMJD1A is 10 times more sensitive to nickel inhibition with an IC(50) [Ni(II)] of 2.5 microm, and approximately one molecule of Ni(II) inhibits one molecule of JMJD1A, suggesting that nickel causes inhibition by replacing the iron. Furthermore, nickel-bound JMJD1A is not reactivated by excessive iron even up to a 2 mm concentration. Using x-ray absorption spectroscopy, we demonstrate that nickel binds to the same site in ABH2 as iron, and replacement of the iron by nickel does not prevent the binding of the cofactor 2-oxoglutarate. Finally, we show that nickel ions target and inhibit JMJD1A in intact cells, and disruption of the iron-binding site decreases binding of nickel ions to ABH2 in intact cells. Together, our results reveal that the members of this dioxygenase family are specific targets for nickel ions in cells. Inhibition of these dioxygenases by nickel is likely to have widespread impacts on cells (e.g. impaired epigenetic programs and DNA repair) and may eventually lead to cancer development.
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Registered trials
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.