ArticleNeurotoxicology2017
Methylmercury augments Nrf2 activity by downregulation of the Src family kinase Fyn.
Article in Neurotoxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Nrf2 and STAT3 Pathways in Protecting Against Methylmercury-Induced Oxidative Stress in Hypothalamic Neuronal GT1-7 Cells.Neurochemical research · 2026Article
- Fyn inhibition by TAE684: A synergistic strategy to suppress melanoma and reverse vemurafenib resistance.Cell death & disease · 2025Article
- JAK2/STAT3 Signaling Pathway Modulates Acute Methylmercury Toxicity in the Mouse Astrocyte C8-D1A Cell Line.Neurochemical research · 2025Article
- KEAP1 polymorphisms and neurodevelopmental outcomes in children with exposure to prenatal MeHg from the Seychelles Child Development Study Nutrition Cohort 2.Neurotoxicology · 2023Article
- Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.Biomolecules · 2022Review
- Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells.Molecular neurobiology · 2022Article
- Effect of Solanum vegetables on memory index, redox status, and expressions of critical neural genes in Drosophila melanogaster model of memory impairment.Metabolic brain disease · 2022Article
- Ziziphus spina-christi leaf extract attenuates mercuric chloride-induced liver injury in male rats via inhibition of oxidative damage.Environmental science and pollution research international · 2021Article
- Tissue-specific Nrf2 signaling protects against methylmercury toxicity in Drosophila neuromuscular development.Archives of toxicology · 2020Article
- CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways.Antioxidants (Basel, Switzerland) · 2020Article
- Methylmercury-Mediated Oxidative Stress and Activation of the Cellular Protective System.Antioxidants (Basel, Switzerland) · 2020Review
- Sulfhydryl groups as targets of mercury toxicity.Coordination chemistry reviews · 2020Article
- Redox toxicology of environmental chemicals causing oxidative stress.Redox biology · 2020Review
- Optogenetic Control for Investigating Subcellular Localization of Fyn Kinase Activity in Single Live Cells.Journal of molecular biology · 2020Article
- Manganese Acts upon Insulin/IGF Receptors to Phosphorylate AKT and Increase Glucose Uptake in Huntington's Disease Cells.Molecular neurobiology · 2020Article
- Nrf2 Activation and Its Coordination with the Protective Defense Systems in Response to Electrophilic Stress.International journal of molecular sciences · 2020Review
- Glutathione antioxidant system and methylmercury-induced neurotoxicity: An intriguing interplay.Biochimica et biophysica acta. General subjects · 2019Review
- Curcumin protects against methylmercury-induced cytotoxicity in primary rat astrocytes by activating the Nrf2/ARE pathway independently of PKCδ.Toxicology · 2019Article
- Post-translational modifications in MeHg-induced neurotoxicity.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Protective Effects ofToxicological research · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Methylmercury (MeHg) is a potent developmental neurotoxicant that induces an oxidative stress response in the brain. It has been demonstrated that MeHg exposure increases nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Nrf2 is a transcription factor that translocates to the nucleus in response to oxidative stress, and upregulates phase II detoxifying enzymes. Although, Nrf2 activity is augmented subsequent to MeHg exposure, it has yet to be established whether Nrf2 moves into the nucleus as a result. Furthermore, the potential effect MeHg might have on the non-receptor tyrosine kinase, Fyn, has not been addressed. Fyn phosphorylates Nrf2 in the nucleus, resulting in its inactivation, and consequent downregulation of the oxidative stress response. Here, we observe Nrf2 translocates to the nucleus subsequent to MeHg-induced oxidative stress. This response is concomitant with reduced Fyn expression and nuclear localization. Moreover, we detected an increase in phosphorylated Akt and glycogen synthase kinase 3 beta (GSK-3β) at activating and inhibitory sites, respectively. Akt phosphorylates and inhibits GSK-3β, which subsequently prevents Fyn phosphorylation to signal nuclear import. Our results demonstrate MeHg downregulates Fyn to maintain Nrf2 activity, and further illuminate a potential mechanism by which MeHg elicits neurotoxicity.
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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.