Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes

Liddell, Jeffrey R.; Zwingmann, Claudia; Schmidt, Maike; Thiessen, Anette; Leibfritz, Dieter; Robinson, Stephen R.; Dringen, Ralf

doi:10.1002/jnr.22093

Cited by 36 publications

(21 citation statements)

References 68 publications

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“…At least, no obvious differences were observed for the basal glycolytic fl ux and for the specifi c activities of some glycolytic enzymes of the two types of culture. The data obtained for glucose consumption rates, lactate release rates and the specifi c activities of GAPDH, LDH or G6PDH of WT and Ctsk −/− cultures were similar to those previously reported for astrocyte cultures (Liddell et al , 2009 ;Tulpule et al , 2010 ;Schmidt et al , 2011 ). Also, the specifi c cellular GSx contents, the GSH export rates as well as the specifi c activity of γ GT, were identical for WT and Ctsk −/− astrocyte cultures, demonstrating that absence of cathepsin K does not affect the basal GSH metabolism or the supply of GSH precursors to neurons, contrasting for example with the situation described for Mrp1-defi cient astrocytes (Minich et al , 2006 ).…”

Section: Discussionmentioning

confidence: 93%

Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice

Dauth¹,

Schmidt²,

Rehders

et al. 2012

Biological Chemistry

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Cathepsin K is important for the brain, because its deficiency in mice is associated with a marked decrease in differentiated astrocytes and changes in neuronal patterning in the hippocampus as well as with learning and memory deficits. As cathepsin K activity is most prominent in hippocampal regions of wild type animals, we hypothesised alterations in astrocyte-mediated support of neurons as a potential mechanism underlying the impaired brain functions in cathepsin K-deficient mice. To address this hypothesis, we have generated and characterised astroglia-rich primary cell cultures from cathepsin K-deficient and wild type mice and compared these cultures for possible changes in metabolic support functions and cell composition. Interestingly, cells expressing the oligodendrocytic markers myelin-associated glycoprotein and myelin basic protein were more frequent in astroglia-rich cultures from cathepsin K-deficient mice. However, cell cultures from both genotypes were morphologically comparable and similar with respect to glucose metabolism. In addition, specific glutathione content, glutathione export and γ-glutamyl-transpeptidase activity remained unchanged, whereas the specific activities of glutathione reductase and glutathione-S-transferase were increased by around 50% in cathepsin K-deficient cultures. Thus, lack of cathepsin K in astroglia-rich cultures appears not to affect metabolic supply functions of astrocytes but to facilitate the maturation of oligodendrocytes.

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Section: Discussionmentioning

confidence: 93%

Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice

Dauth¹,

Schmidt²,

Rehders

et al. 2012

Biological Chemistry

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“…The concentrations of extracellular lactate and glucose were determined by coupled enzymatic assays as described previously [40,44]. The amount of glucose consumed was calculated as difference between the glucose content of the incubation medium harvested after a given incubation and the medium applied to the cells.…”

Section: Determination Of Lactate Glucose and Glutathionementioning

confidence: 99%

Copper Oxide Nanoparticles Stimulate Glycolytic Flux and Increase the Cellular Contents of Glutathione and Metallothioneins in Cultured Astrocytes

Bulcke

Dringen

2014

Neurochem Res

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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.

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“…Extracellular lactate concentration in culture media was determined using a modification of an established assay (Dringen et al 1993;Liddell et al 2009). In brief, 20 ll media sample was diluted with 160 ll purified water in wells of a microtiter plate and mixed with 180 ll reaction mixture (5.6 mM NAD ?…”

Section: Determination Of Lactate In Culture Mediummentioning

confidence: 99%

Effects of Chlorinated Acetates on the Glutathione Metabolism and on Glycolysis of Cultured Astrocytes

2010

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The chlorinated acetates monochloroacetate (MCA), dichloroacetate (DCA), and trichloroacetate (TCA) are generated in water disinfection processes and are formed during metabolic detoxification of industrial solvents such as trichloroethylene. In order to test for consequences of an exposure of brain cells to the different chlorinated acetates, glutathione levels and lactate production of primary astrocyte cultures were investigated as indicators for the potential of chlorinated acetates to disturb cellular detoxification processes and glucose metabolism, respectively. Application of MCA to cultured astrocytes caused a time and concentration dependent deprivation of cellular glutathione, inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, and loss in cell viability with halfmaximal effects observed for MCA concentrations between 0.3 and 3 mM. In contrast, the presence of acetate, DCA, or TCA in a concentration of 10 mM did not compromise cell viability nor affect cellular glutathione content or GAPDH activity. However, the presence of DCA and TCA significantly lowered the rate of cellular lactate production in viable astrocytes. These data demonstrate that the extent of chlorination strongly determines the potential of chlorinated acetates to disturb glutathione and/or glucose metabolism of astrocytes.

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Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes

Cited by 36 publications

References 68 publications

Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice

Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice

Copper Oxide Nanoparticles Stimulate Glycolytic Flux and Increase the Cellular Contents of Glutathione and Metallothioneins in Cultured Astrocytes

Effects of Chlorinated Acetates on the Glutathione Metabolism and on Glycolysis of Cultured Astrocytes

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