ArticleScientific reports2016
Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of the Various Effect of Arsenic on Glutathione Synthesis In Vitro and In Vivo.BioMed research international · 2020Pooled it
- Sulfur-Containing Amino Acid Homeostasis in the Central Nervous System: From Physiology Regulation to Metal-Induced Neurotoxicity.Metabolites · 2026Review
- Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction.Frontiers in behavioral neuroscience · 2026Review
- Arsenic-Induced Polyneuropathy Mimicking Guillain-Barré Syndrome: A Conundrum.Clinical case reports · 2025Article
- Article
- The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice.Brain sciences · 2023Article
- Article
- Arsenic-induced neurotoxicity: a mechanistic appraisal.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Review
- Attenuated glutamate induced ROS production by antioxidative compounds in neural cell lines.RSC advances · 2019Article
- Anti-oxidative effects of catechins and theaflavins on glutamate-induced HT22 cell damage.RSC advances · 2019Article
- The role of glial-neuronal metabolic cooperation in modulating progression of multiple sclerosis and neuropathic pain.Immunotherapy · 2019Review
- Sneaky Entry of IFNγ Through Arsenic-Induced Leaky Blood-Brain Barrier Reduces CD200 Expression by Microglial pro-Inflammatory Cytokine.Molecular neurobiology · 2019Article
- Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.Antioxidants & redox signaling · 2018Review
- Fluorometric Estimation of Glutathione in Cultured Microglial Cell Lysate.Bio-protocol · 2017Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc(-) (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons.
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