title: Copper oxide nanoparticles stimulate glycolytic flux and increase the cellular contents of glutathione and metallothioneins in cultured astrocytes.
abstract: Copper oxide nanoparticles (CuO-NPs) are frequently used for industrial or medical applications and are known for their high toxic potential. As little is known so far on the consequences of an exposure of brain cells to such particles, we applied CuO-NPs to cultured primary rat astrocytes and investigated whether such particles affect cell viability and alter their metabolic properties. Astrocytes efficiently accumulated CuO-NPs in a time- and concentration-dependent manner. The cells remained viable during a 24 h incubation with 100 µM copper in the form of CuO-NPs, while higher concentrations of CuO-NPs severely compromised the cell viability. Astrocytes that were exposed for 24 h to 100 µM CuO-NPs showed significantly enhanced extracellular lactate concentrations and increased cellular levels of glutathione and metallothioneins. The CuO-NP-induced increase in lactate release and metallothionein content were prevented by the presence of the membrane-permeable copper chelator tetrathiomolybdate, while this chelator increased already in the absence of CuO-NPs the cellular glutathione content. After removal of the CuO-NPs following a 24 h pre-incubation with 100 µM CuO-NPs, astrocytes maintained during a further 6 h incubation an elevated glycolytic lactate release and exported significantly more glutathione than control cells that had been pre-incubated without CuO-NPs. These data suggest that copper ions which are liberated from internalized CuO-NPs stimulate glycolytic flux as well as the synthesis of glutathione and metallothioneins in cultured viable astrocytes.
authors.affiliation: Center for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, P.O. Box 330440, 28334, Bremen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bulcke
authors.forename: Ralf
authors.initials: R
authors.lastname: Dringen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D008668:Metallothionein / Q000378:metabolism*; D053758:Nanoparticles / Q000378:metabolism / Q000633:toxicity; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002614:Chelating Agents; D003300:Copper; D008668:Metallothionein; D005978:Glutathione; C000520:cuprous oxide