ArticleNeurotoxicology2013
The Nrf2/SKN-1-dependent glutathione S-transferase π homologue GST-1 inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of manganism.
Article in Neurotoxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- MGST3 Promotes Endometriosis Progression by Suppressing Ferroptosis.Cell biochemistry and biophysics · 2026Article
- The Inhibition of Fatty Acid Amide Hydrolase-4 Affords Neuroprotection in a Toxic Model Induced by 6-Hydroxydopamine in Caenorhabditis elegans Nematodes.Molecular neurobiology · 2025Article
- Strain-specific effects of Desulfovibrio on neurodegeneration and oxidative stress in a Caenorhabditis elegans PD model.NPJ Parkinson's disease · 2025Article
- Combined Restraint Stress and Metal Exposure Paradigms in Rats: Unravelling Behavioural and Neurochemical Perturbations.Molecular neurobiology · 2025Article
- Biofilm proficient Bacillus subtilis prevents neurodegeneration in Caenorhabditis elegans Parkinson's disease models via PMK-1/p38 MAPK and SKN-1/Nrf2 signaling.Scientific reports · 2025Article
- Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function.The Journal of cell biology · 2025Article
- Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript.Metallomics : integrated biometal science · 2024Article
- The Role of Oxidative Stress in Manganese Neurotoxicity: A Literature Review Focused on Contributions Made by Professor Michael Aschner.Biomolecules · 2023Review
- Applications of a powerful model organism Caenorhabditis elegans to study the neurotoxicity induced by heavy metals and pesticides.Physiological research · 2023Article
- Article
- Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span ofFrontiers in pharmacology · 2022Article
- Assessment of the effects of organic vs. inorganic arsenic and mercury inCurrent research in toxicology · 2022Article
- Neurotoxicity mechanisms of manganese in the central nervous system.Advances in neurotoxicology · 2021Article
- The glutathione system and the related thiol network in Caenorhabditis elegans.Redox biology · 2019Review
- Inhibition of glutathione S-transferase-pi triggers c-jun N-terminal kinase-dependent neuronal death in Zn-induced Parkinsonism.Molecular and cellular biochemistry · 2019Article
- Acute exposure to a glyphosate-containing herbicide formulation inhibits Complex II and increases hydrogen peroxide in the model organism Caenorhabditis elegans.Environmental toxicology and pharmacology · 2019Article
- Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity.Neurotoxicity research · 2018Article
- C. elegans as a model in developmental neurotoxicology.Toxicology and applied pharmacology · 2018Review
- Toxicity interactions between manganese (Mn) and lead (Pb) or cadmium (Cd) in a model organism the nematode C. elegans.Environmental science and pollution research international · 2018Article
- Mutations in Caenorhabditis elegans neuroligin-like glit-1, the apoptosis pathway and the calcium chaperone crt-1 increase dopaminergic neurodegeneration after 6-OHDA treatment.PLoS genetics · 2018Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Exposure to high levels of manganese (Mn) results in a neurological condition termed manganism, which is characterized by oxidative stress, abnormal dopamine (DA) signaling, and cell death. Epidemiological evidence suggests correlations with occupational exposure to Mn and the development of the movement disorder Parkinson's disease (PD), yet the molecular determinants common between the diseases are ill-defined. Glutathione S-transferases (GSTs) of the class pi (GSTπ) are phase II detoxification enzymes that conjugate both endogenous and exogenous compounds to glutathione to reduce cellular oxidative stress, and their decreased expression has recently been implicated in PD progression. In this study we demonstrate that a Caenorhabditis elegans GSTπ homologue, GST-1, inhibits Mn-induced DA neuron degeneration. We show that GST-1 is expressed in DA neurons, Mn induces GST-1 gene and protein expression, and GST-1-mediated neuroprotection is dependent on the PD-associated transcription factor Nrf2/SKN-1, as a reduction in SKN-1 gene expression results in a decrease in GST-1 protein expression and an increase in DA neuronal death. Furthermore, decreases in gene expression of the SKN-1 inhibitor WDR-23 or the GSTπ-binding cell death activator JNK/JNK-1 result in an increase in resistance to the metal. Finally, we show that the Mn-induced DA neuron degeneration is independent of the dopamine transporter DAT, but is largely dependent on the caspases CED-3 and the novel caspase CSP-1. This study identifies a C. elegans Nrf2/SKN-1-dependent GSTπ homologue, cell death effectors of GSTπ-associated xenobiotic-induced pathology, and provides the first in vivo evidence that a phase II detoxification enzyme may modulate DA neuron vulnerability in manganism.
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