ArticleNeurochemical research2019
Exposure of Cultured Astrocytes to Menadione Triggers Rapid Radical Formation, Glutathione Oxidation and Mrp1-Mediated Export of Glutathione Disulfide.
Article in Neurochemical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 27 citations in OpenAlex.
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- Glutathione Metabolism of the Brain-The Role of Astrocytes.Journal of neurochemistry · 2025Review
- Differential Effects of Itaconate and its Esters on the Glutathione and Glucose Metabolism of Cultured Primary Rat Astrocytes.Neurochemical research · 2024Article
- Modulation of Multidrug Resistance Protein 1-mediated Transport Processes by the Antiviral Drug Ritonavir in Cultured Primary Astrocytes.Neurochemical research · 2024Article
- β-lapachone-mediated WST1 Reduction as Indicator for the Cytosolic Redox Metabolism of Cultured Primary Astrocytes.Neurochemical research · 2023Article
- Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies.Frontiers in immunology · 2022Review
- Investigating the antimicrobial, antioxidant and cytotoxic activities of the biological synthesized glutathione selenium nano-incorporation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Confined growth of ZIF-8 in dendritic mesoporous organosilica nanoparticles as bioregulators for enhanced mRNA deliveryNational science review · 2021Article
- The Menadione-Mediated WST1 Reduction by Cultured Astrocytes Depends on NQO1 Activity and Cytosolic Glucose Metabolism.Neurochemical research · 2021Article
- In vitro function and in situ localization of Multidrug Resistance-associated Protein (MRP)1 (ABCC1) suggest a protective role against methyl mercury-induced oxidative stress in the human placenta.Archives of toxicology · 2020Article
- β-Lapachone Induces Acute Oxidative Stress in Rat Primary Astrocyte Cultures that is Terminated by the NQO1-Inhibitor Dicoumarol.Neurochemical research · 2020Article
- Interactions of TiOChemical research in toxicology · 2020Article
- Oxidative Stress Induction Is a Rational Strategy to Enhance the Productivity ofJournal of agricultural and food chemistry · 2020Article
- GATA-1 isoforms differently contribute to the production and compartmentation of reactive oxygen species in the myeloid leukemia cell line K562.Journal of cellular physiology · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Menadione (2-methyl-1,4-naphthoquinone) is a synthetic derivative of vitamin K that allows rapid redox cycling in cells and thereby generates reactive oxygen species (ROS). To test for the consequences of a treatment of brain astrocytes with menadione, we incubated primary astrocyte cultures with this compound. Incubation with menadione in concentrations of up to 30 µM did not affect cell viability. In contrast, exposure of astrocytes to 100 µM menadione caused a time-dependent impairment of cellular metabolism and cell functions as demonstrated by impaired glycolytic lactate production and strong increases in the activity of extracellular lactate dehydrogenase and in the number of propidium iodide-positive cells within 4 h of incubation. In addition, already 5 min after exposure of astrocytes to menadione a concentration-dependent increase in the number of ROS-positive cells as well as a concentration-dependent and transient accumulation of cellular glutathione disulfide (GSSG) were observed. The rapid intracellular GSSG accumulation was followed by an export of GSSG that was prevented in the presence of MK571, an inhibitor of the multidrug resistance protein 1 (Mrp1). Menadione-induced glutathione (GSH) oxidation and ROS formation were found accelerated after glucose-deprivation, while the presence of dicoumarol, an inhibitor of the menadione-reducing enzyme NQO1, did not affect the menadione-dependent GSSG accumulation. Our study demonstrates that menadione rapidly depletes cultured astrocytes of GSH via ROS-induced oxidation to GSSG that is subsequently exported via Mrp1.
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