ArticleMolecular psychiatry2004
Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal.
Article in Molecular psychiatry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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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
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Systemic review of genetic and epigenetic factors underlying differential toxicity to environmental lead (Pb) exposure.Environmental science and pollution research international · 2022Pooled it
- Systemic review of the epidemiology of autism in Arab Gulf countries.Neurosciences (Riyadh, Saudi Arabia) · 2014Pooled it
- Sulfur-Containing Amino Acid Homeostasis in the Central Nervous System: From Physiology Regulation to Metal-Induced Neurotoxicity.Metabolites · 2026Review
- Zebrafish parental co-exposure to environmentally relevant levels of inorganic arsenic + methylmercury impacts neurobehavior in parents and progeny.Environmental toxicology and pharmacology · 2026Article
- Fingolimod normalizes metabolic signatures associated with synaptic plasticity and memory in APP/PS1 model: Sphingosine-1-phosphate receptor a therapeutic target for Alzheimer's.Scientific reports · 2026Article
- Article
- Rescue of hippocampal synaptic plasticity and memory performance by Fingolimod (FTY720) in APP/PS1 model of Alzheimer's disease is accompanied by correction in metabolism of sphingolipids, polyamines, and phospholipid saturation composition.bioRxiv : the preprint server for biology · 2025Article
- Comparative Phosphoproteomics of Neuro-2a Cells under Insulin Resistance Reveals New Molecular Signatures of Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Toxoplasmosis: Targeting neurotransmitter systems in psychiatric disorders.Metabolic brain disease · 2022Review
- Epigenetic influence of environmentally neurotoxic metals.Neurotoxicology · 2020Review
- Sex difference in the progression of manic symptoms during acute hospitalization: A prospective pilot study.Brain and behavior · 2020Article
- Methylation-related metabolic effects of D4 dopamine receptor expression and activation.Translational psychiatry · 2019Article
- Alterations in folate-dependent one-carbon metabolism as colon cell transition from normal to cancerous.The Journal of nutritional biochemistry · 2019Article
- Components of the folate metabolic pathway and ADHD core traits: an exploration in eastern Indian probands.Journal of human genetics · 2017Article
- Redox-Related Epigenetic Mechanisms in Glioblastoma: Nuclear Factor (Erythroid-Derived 2)-Like 2, Cobalamin, and Dopamine Receptor Subtype 4.Frontiers in oncology · 2017Article
- Mean serum-level of common organic pollutants is predictive of behavioral severity in children with autism spectrum disorders.Scientific reports · 2016Article
- Article
- A quantitative proteomic approach for unveiling novel mechanisms associated with MeHg-induced toxicity: effects on the methylation cycle.Toxicology research · 2016Article
- Neuregulin 1 Promotes Glutathione-Dependent Neuronal Cobalamin Metabolism by Stimulating Cysteine Uptake.Oxidative medicine and cellular longevity · 2016Article
- Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal.Oxidative medicine and cellular longevity · 2016Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylation events play a critical role in the ability of growth factors to promote normal development. Neurodevelopmental toxins, such as ethanol and heavy metals, interrupt growth factor signaling, raising the possibility that they might exert adverse effects on methylation. We found that insulin-like growth factor-1 (IGF-1)- and dopamine-stimulated methionine synthase (MS) activity and folate-dependent methylation of phospholipids in SH-SY5Y human neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent mechanism. The stimulation of this pathway increased DNA methylation, while its inhibition increased methylation-sensitive gene expression. Ethanol potently interfered with IGF-1 activation of MS and blocked its effect on DNA methylation, whereas it did not inhibit the effects of dopamine. Metal ions potently affected IGF-1 and dopamine-stimulated MS activity, as well as folate-dependent phospholipid methylation: Cu(2+) promoted enzyme activity and methylation, while Cu(+), Pb(2+), Hg(2+) and Al(3+) were inhibitory. The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC(50) of 1 nM and eliminated MS activity. Our findings outline a novel growth factor signaling pathway that regulates MS activity and thereby modulates methylation reactions, including DNA methylation. The potent inhibition of this pathway by ethanol, lead, mercury, aluminum and thimerosal suggests that it may be an important target of neurodevelopmental toxins.
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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.