Arsenite interrupts neurodevelopmental processes of human and rat neural progenitor cells: The role of reactive oxygen species and species-specific antioxidative defense

Autor: Stefan Masjosthusmann, Ellen Fritsche, Farina Bendt, Jenny Baumann, Clara Siebert, Ulrike Hübenthal
Rok vydání: 2019
Předmět:
Environmental Engineering
Sodium arsenite
Arsenites
Neurogenesis
Health
Toxicology and Mutagenesis
0208 environmental biotechnology
02 engineering and technology
010501 environmental sciences
medicine.disease_cause
01 natural sciences
Antioxidants
Hazardous Substances
Arsenic
chemistry.chemical_compound
Species Specificity
Toxicity Tests
medicine
Animals
Humans
Environmental Chemistry
0105 earth and related environmental sciences
Arsenite
Neurons
chemistry.chemical_classification
Reactive oxygen species
Stem Cells
Public Health
Environmental and Occupational Health
Oligodendrocyte differentiation
General Medicine
General Chemistry
Glutathione
Sodium Compounds
Pollution
Oligodendrocyte
Acetylcysteine
Rats
020801 environmental engineering
Cell biology
Oxidative Stress
medicine.anatomical_structure
chemistry
Reactive Oxygen Species
Heme Oxygenase-1
Oxidative stress
Zdroj: Chemosphere. 235:447-456
ISSN: 0045-6535
Popis: Arsenic exposure disturbs brain development in humans. Although developmental neurotoxicity (DNT) of arsenic has been studied in vivo and in vitro, its mode-of-action (MoA) is not completely understood. Here, we characterize the adverse neurodevelopmental effects of sodium arsenite on developing human and rat neural progenitor cells (hNPC, rNPC). Moreover, we analyze the involvement of reactive oxygen species (ROS) and the role of the glutathione (GSH)-dependent antioxidative defense for arsenite-induced DNT in a species-specific manner. We determined IC50 values for sodium arsenite-dependent (0.1–10 μM) inhibition of hNPC and rNPC migration (6.0 μM; >10 μM), neuronal (2.7 μM; 4.4 μM) and oligodendrocyte (1.1 μM; 2.0 μM) differentiation. ROS involvement was studied by quantifying the expression of ROS-regulated genes, measuring glutathione (GSH) levels, inhibiting GSH synthesis and co-exposing cells to the antioxidant N-acetylcysteine. Arsenite reduces NPC migration, neurogenesis and oligodendrogenesis of differentiating hNPC and rNPC at sub-cytotoxic concentrations. Species-specific arsenite cytotoxicity and induction of antioxidative gene expression is inversely related to GSH levels with rNPC possessing >3-fold the amount of GSH than hNPC. Inhibition of GSH synthesis increased the sensitivity towards arsenite in rNPC > hNPC. N-acetylcysteine antagonized arsenite-mediated induction of HMOX1 expression as well as reduction of neuronal and oligodendrocyte differentiation in hNPC suggesting involvement of oxidative stress in arsenite DNT. hNPC are more sensitive towards arsenite-induced neurodevelopmental toxicity than rNPC, probably due to their lower antioxidative defense capacities. This species-specific MoA data might be useful for adverse outcome pathway generation and future integrated risk assessment strategies concerning DNT.
Databáze: OpenAIRE
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