Iron- and 2-oxoglutarate-dependent Dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity
- 19 December 2008
- journal article
- research article
- Published by Springer Nature in BioMetals
- Vol. 22 (1), 191-196
- https://doi.org/10.1007/s10534-008-9190-3
Abstract
Nickel compounds are important occupational and environmental pollutants. Chronic exposure to these pollutants has been connected with increased risks of respiratory cancers and cardiovascular diseases. However, it is still not clear what are the specific molecular targets for nickel toxicity and carcinogenicity. Here, we propose that the iron- and 2-oxoglutarate-dependent dioxygenase family enzymes are important intracellular targets that mediate the toxicity and carcinogenicity of nickel. In support of this hypothesis, our data show that three different classes of enzymes in this iron- and 2-oxoglutarate-dependent dioxygenase family, including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA repair enzyme ABH3, are all highly sensitive to nickel inhibition. Inactivation of these enzymes accounts for a number of deleterious effects caused by nickel in cells, namely hypoxia-mimic stress and aberrant epigenetic changes. Future studies on nickel’s effects on these iron- and 2-oxoglutarate-dependent dioxygenases would deepen our understanding on nickel toxicity and carcinogenicity.Keywords
This publication has 36 references indexed in Scilit:
- Systemic Iron Homeostasis and the Iron-Responsive Element/Iron-Regulatory Protein (IRE/IRP) Regulatory NetworkAnnual Review of Nutrition, 2008
- Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNANature, 2008
- Regulation of histone methylation by demethylimination and demethylationNature Reviews Molecular Cell Biology, 2007
- Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damageThe EMBO Journal, 2006
- Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)Proceedings of the National Academy of Sciences, 2006
- Structural Insights into Histone Demethylation by JMJD2 Family MembersCell, 2006
- Nickel Ions Increase Histone H3 Lysine 9 Dimethylation and Induce Transgene SilencingMolecular and Cellular Biology, 2006
- JHDM2A, a JmjC-Containing H3K9 Demethylase, Facilitates Transcription Activation by Androgen ReceptorCell, 2006
- Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cellsToxicology and Applied Pharmacology, 2005
- Nickel carcinogenesis: Epigenetics and hypoxia signalingMutation Research, 2005