Arsenate Stimulates Glutathione Export from Viable Cultured Rat Cerebellar Granule Neurons

Arsenate is an environmental pollutant which contaminates the drinking water of millions of people worldwide. Numerous in vitro studies have investigated the toxicity of arsenate for a large number of different cell types. However, despite the known neurotoxic potential of arsenicals, little is know...

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Bibliographic Details
Published in:Neurochemical research 2015-03, Vol.40 (3), p.561-571
Main Authors: Hohnholt, Michaela C., Blumrich, Eva-Maria, Koehler, Yvonne, Dringen, Ralf
Format: Article
Language:English
Subjects:
Animals
Arsenates - pharmacology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Survival - drug effects
Cell Survival - physiology
Cells, Cultured
Cerebellum - cytology
Cerebellum - drug effects
Cerebellum - secretion
Dose-Response Relationship, Drug
Glutathione - secretion
Neurochemistry
Neurology
Neurons - drug effects
Neurons - secretion
Neurosciences
Original Paper
Rats
Rats, Wistar
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Summary:Arsenate is an environmental pollutant which contaminates the drinking water of millions of people worldwide. Numerous in vitro studies have investigated the toxicity of arsenate for a large number of different cell types. However, despite the known neurotoxic potential of arsenicals, little is known so far about the consequences of an exposure of neurons to arsenate. To investigate acute effects of arsenate on the viability and the glutathione (GSH) metabolism of neurons, we have exposed primary rat cerebellar granule neuron cultures to arsenate. Incubation of neurons for up to 6 h with arsenate in concentrations of up to 10 mM did not acutely compromise the cell viability, although the cells accumulated substantial amounts of arsenate. However, exposure to arsenate caused a time- and concentration-dependent increase in the export of GSH from viable neurons with significant effects observed for arsenate in concentrations above 0.3 mM. The arsenate-induced stimulation of GSH export was abolished upon removal of arsenate and completely prevented by MK571, an inhibitor of the multidrug resistance protein 1. These results demonstrate that arsenate is not acutely toxic to neurons but can affect the neuronal GSH metabolism by stimulating GSH export.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-014-1501-1