ArticleEnvironmental health perspectives2010
Arsenic inhibits neurite outgrowth by inhibiting the LKB1-AMPK signaling pathway.
Article in Environmental health perspectives, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 88 citations in OpenAlex.
- Changes in Energy Dynamics in Arsenic Exposure based Neurotoxicity: A Comprehensive Review.Current medicinal chemistry · 2025Review
- Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.Journal of hazardous materials · 2024Article
- Arsenic Impairs Differentiation of Human Induced Pluripotent Stem Cells into Cholinergic Motor Neurons.Toxics · 2023Article
- Arsenic impairs stem cell differentiation via the Hippo signaling pathway.Toxicology research · 2023Article
- High-Throughput Neurite Outgrowth Assay Using GFP-Labeled iPSC-Derived Neurons.Current protocols · 2022Article
- Perfluorooctanesulfonic Acid (PFOS) Thwarts the Beneficial Effects of Calorie Restriction and Metformin.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Long-term arsenic exposure impairs differentiation in mouse embryonal stem cells.Journal of applied toxicology : JAT · 2021Article
- Evaluation of chemical compounds that inhibit neurite outgrowth using GFP-labeled iPSC-derived human neurons.Neurotoxicology · 2021Article
- Role of metallic pollutants in neurodegeneration: effects of aluminum, lead, mercury, and arsenic in mediating brain impairment events and autism spectrum disorder.Environmental science and pollution research international · 2021Review
- Resveratrol Attenuates Learning, Memory, and Social Interaction Impairments in Rats Exposed to Arsenic.BioMed research international · 2021Article
- Cathepsin B inhibition blocks neurite outgrowth in cultured neurons by regulating lysosomal trafficking and remodeling.Journal of neurochemistry · 2020Article
- Curcumin supplementation shows modulatory influence on functional and morphological features of hippocampus in mice subjected to arsenic trioxide exposure.Anatomy & cell biology · 2020Article
- Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies.International journal of molecular sciences · 2020Review
- Arsenic Toxicity: Molecular Targets and Therapeutic Agents.Biomolecules · 2020Review
- The Adiponectin Homolog Osmotin Enhances Neurite Outgrowth and Synaptic Complexity via AdipoR1/NgR1 Signaling in Alzheimer's Disease.Molecular neurobiology · 2018Article
- Increased frequency of AMP-activated protein kinase-positive spinal motor neurons after sciatic nerve injury in a mouse model.The Kaohsiung journal of medical sciences · 2018Article
- mTOR/AMPK signaling in the brain: Cell metabolism, proteostasis and survival.Current opinion in toxicology · 2018Article
- Arsenic Induces Members of the mmu-miR-466-669 Cluster Which Reduces NeuroD1 Expression.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury.Scientific reports · 2017Article
- Differential epigenetic effects of chlorpyrifos and arsenic in proliferating and differentiating human neural progenitor cells.Reproductive toxicology (Elmsford, N.Y.) · 2016Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundArsenic (As) is an environmental pollutant that induces numerous pathological effects, including neurodevelopmental disorders. OBJECTIVES AND
methodsWe evaluated the role of the LKB1-AMPK pathway in As-induced developmental neurotoxicity using Neuro-2a (N2a) neuroblastoma cells as a model of developing neurons.
resultsThe addition of low concentrations of As (<or= 5 microM) during differentiation caused an inhibitory effect on the neurite outgrowth in N2a cells in the absence of cell death. Activation of adenosine monophosphate-activated kinase (AMPK) induced by retinoic acid in differentiating cells was blocked by As. Pretreatment with the AMPK-specific activator 5-aminoimidazole-4-carboxamide riboside or overexpression of a constitutively active AMPK-alpha1 plasmid reversed As-induced inhibition of neurite outgrowth. The activation of LKB1 (serine/threonine kinase 11), a major AMPK kinase, was also suppressed by As by inhibiting both the phosphorylation and the translocation of LKB1 from nucleus to cytoplasm. Antioxidants, such as N-acetyl cysteine and superoxide dismutase, but not catalase, protected against As-induced inactivation of the LKB1-AMPK pathway and reversed the inhibitory effect of As on neurite outgrowth.
conclusionsReduced neurite outgrowth induced by As results from deficient activation of AMPK as a consequence of a lack of activation of LKB1. Oxidative stress induced by As, especially excessive superoxide, plays a critical role in blocking the LKB1-AMPK pathway. Our studies provide insight into the mechanisms underlying As-induced developmental neurotoxicity, which is important for designing a new strategy for protecting children against this neurotoxic substance.
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