Adsorption and orientation of the physiological extracellular peptide glutathione disulfide on surface functionalized colloidal alumina particles.

Understanding the interrelation between surface chemistry of colloidal particles and surface adsorption of biomolecules is a crucial prerequisite for the design of materials for biotechnological and nanomedical applications. Here, we elucidate how tailoring the surface chemistry of colloidal alumina particles (d50 = 180 nm) with amino (-NH2), carboxylate (-COOH), phosphate (-PO3H2) or sulfonate (-SO3H) groups affects adsorption and orientation of the model peptide glutathione disulfide (GSSG). GSSG adsorbed on native, -NH2-functionalized, and -SO3H-functionalized alumina but not on -COOH- and -PO3H2-functionalized particles.

Formaldehyde induces rapid glutathione export from viable oligodendroglial OLN-93 cells.

Formaldehyde is a neurotoxic environmental pollutant that can also be produced in the body by certain enzymatic reactions. To test for the potential consequences of an exposure of oligodendrocytes to formaldehyde, we used OLN-93 cells as a model system. Treatment with formaldehyde altered the cellular glutathione (GSH) content of these cells by inducing a rapid time- and concentration-dependent export of GSH.

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

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.

Deep carbon export from a Southern Ocean iron-fertilized diatom bloom.

Fertilization of the ocean by adding iron compounds has induced diatom-dominated phytoplankton blooms accompanied by considerable carbon dioxide drawdown in the ocean surface layer. However, because the fate of bloom biomass could not be adequately resolved in these experiments, the timescales of carbon sequestration from the atmosphere are uncertain. Here we report the results of a five-week experiment carried out in the closed core of a vertically coherent, mesoscale eddy of the Antarctic Circumpolar Current, during which we tracked sinking particles from the surface to the deep-sea floor.

Upregulation of metallothioneins after exposure of cultured primary astrocytes to silver nanoparticles.

To test for the prolonged consequences of a short transient exposure of astrocytes to silver nanoparticles (AgNP), cultured primary astrocytes were incubated for 4 h in the presence of AgNP and the cell viability as well as various metabolic parameters were investigated during a subsequent incubation in AgNP-free medium. Acute exposure of astrocytes to AgNP led to a concentration-dependent increase in the specific cellular silver content to up to 46 nmol/mg protein, but did not compromise cell viability. During a subsequent incubation of the cells in AgNP-free medium, the cellular silver content of AgNP-treated astrocytes remained almost constant for up to 7 days.

Copper export from cultured astrocytes.

Copper is an essential trace metal that is required as a catalytic co-factor or a structural component of several important enzymes. However, since excess of copper can also harm cells due to its potential to catalyse the generation of toxic reactive oxygen species, transport of copper and the cellular copper content are tightly regulated. Astrocytes are known to efficiently take up copper ions, but it was not known whether these cells are also able to export copper.

Magnetic field-induced acceleration of the accumulation of magnetic iron oxide nanoparticles by cultured brain astrocytes.

Magnetic iron oxide nanoparticles (Fe-NPs) are considered for various biomedical and neurobiological applications that involve the presence of external magnetic fields. However, little is known on the effects of a magnetic field on the uptake of such particles by brain cells. Cultured brain astrocytes accumulated dimercaptosuccinate-coated Fe-NP in a time-, temperature-, and concentration-dependent manner.

The antiretroviral protease inhibitors indinavir and nelfinavir stimulate Mrp1-mediated GSH export from cultured brain astrocytes.

Combinations of antiretroviral drugs are successfully used for the treatment of acquired immune deficiency syndrome and reduce the incidence of severe human immunodeficiency virus (HIV)-associated dementia. To test whether such drugs affect the GSH metabolism of brain cells, we have exposed astrocyte-rich primary cultures to various antiretroviral compounds. Treatment of the cultures with the protease inhibitors indinavir or nelfinavir in low micromolar concentrations resulted in a time- and concentration-dependent depletion of cellular GSH from viable cells which was accompanied by a matching increase in the extracellular GSH content.

Adsorption and reduction of glutathione disulfide on α-Al2O3 nanoparticles: experiments and modeling.

Glutathione disulfide (GSSG; γ-GluCysGly disulfide) was used as a physiologically relevant model molecule to investigate the fundamental adsorption mechanisms of polypeptides onto α-alumina nanoparticles. Its adsorption/desorption behavior was studied by enzymatic quantification of the bound GSSG combined with zeta potential measurements of the particles. The adsorption of GSSG to alumina nanoparticles was rapid, was prevented by alkaline pH, was reversed by increasing ionic strength, and followed a nearly ideal Langmuir isotherm with a standard Gibbs adsorption energy of -34.

Exploring uncoupling proteins and antioxidant mechanisms under acute cold exposure in brains of fish.

Exposure to fluctuating temperatures accelerates the mitochondrial respiration and increases the formation of mitochondrial reactive oxygen species (ROS) in ectothermic vertebrates including fish. To date, little is known on potential oxidative damage and on protective antioxidative defense mechanisms in the brain of fish under cold shock. In this study, the concentration of cellular protein carbonyls in brain was significantly increased by 38% within 1 h after cold exposure (from 28 °C to 18 °C) of zebrafish (Danio rerio).

Metabolic and physiological responses in tissues of the long-lived bivalve Arctica islandica to oxygen deficiency.

In Arctica islandica, a long lifespan is associated with low metabolic activity, and with a pronounced tolerance to low environmental oxygen. In order to study metabolic and physiological responses to low oxygen conditions vs. no oxygen in mantle, gill, adductor muscle and hemocytes of the ocean quahog, specimens from the German Bight were maintained for 3.

2-deoxyribose deprives cultured astrocytes of their glutathione.

High concentrations of 2-deoxy-D-ribose (2dRib) have been reported to cause oxidative stress and to disturb the glutathione (GSH) metabolism of various cell types. Exposure of astrocyte-rich primary cultures to millimolar concentrations of 2dRib or its stereoisomer 2-deoxy-L-ribose, but not the incubation with ribose, 2-deoxyglucose, glucose, fructose or saccharose, lowered the cellular GSH content in a time and concentration dependent manner. After exposure for 4 h to 30 mM 2dRib the cells contained 2dRib in a concentration of about 24 mM.

Effects of chlorinated acetates on the glutathione metabolism and on glycolysis of cultured astrocytes.

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.

Zinc prevents the copper-induced damage of cultured astrocytes.

Copper is essential for several cellular processes, but an excess of cellular copper is known to be cell toxic. To study the consequences of a copper treatment of astrocytes, we have used astrocyte-rich primary cultures as model system to investigate cellular functions and cellular integrity of these cells after application of micromolar concentrations of copper chloride. After exposure of the cells to copper, the cell-associated copper content increased strongly in a time and concentration dependent manner.

Fumaric acid dialkyl esters deprive cultured rat oligodendroglial cells of glutathione and upregulate the expression of heme oxygenase 1.

Fumaric acid esters (FAE) are currently tested in clinical studies for their potential to treat multiple sclerosis. Since cellular glutathione is involved in the detoxification of xenobiotics and has been reported to form conjugates with FAE, we have analysed the consequences of an application of various FAE to oligodendroglial cells, using the oligodendroglial cell line OLN-93 and oligodendroglia-rich secondary cultures as model systems. In a concentration of 100 microM, dimethylfumarate (DMF) and diethylfumarate (DEF), but not fumarate nor the monoalkyl esters monomethylfumarate or monoethylfumarate, almost completely deprived both OLN-93 cells and secondary oligodendroglial cultures within 60 min of their cellular glutathione.

Fumaric acid diesters deprive cultured primary astrocytes rapidly of glutathione.

Fumaric acid esters (FAE) are used for the systemic therapy of psoriasis and are now considered for the treatment of autoimmune-based neurological disorders such as multiple sclerosis. Currently, the cellular metabolism of FAE as well as the mechanisms of their therapeutic action are poorly understood. Since cellular glutathione (GSH) is involved in the detoxification of xenobiotics, we analysed the consequences of an application of FAE on the content of GSH in brain cells using astroglia-rich primary cultures as model system.

Differential effects of iodoacetamide and iodoacetate on glycolysis and glutathione metabolism of cultured astrocytes.

Iodoacetamide (IAA) and iodoacetate (IA) have frequently been used to inhibit glycolysis, since these compounds are known for their ability to irreversibly inhibit the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). However, the consequences of a treatment with such thiol reagents on the glutathione (GSH) metabolism of brain cells have not been explored. Exposure of astroglia-rich primary cultures to IAA or IA in concentrations of up to 1 mM deprived the cells of GSH, inhibited cellular GAPDH activity, lowered cellular lactate production and caused a delayed cell death that was detectable after 90 min of incubation.

Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes.

Oxidative stress and disrupted energy metabolism are common to many pathological conditions of the brain. Because astrocytes play an important role in the glucose metabolism of the brain, we have investigated whether sustained oxidative stress affects astroglial glucose metabolism with cultured primary rat astrocytes as a model system. Cultured astrocytes were exposed to a sustained concentration of approximately 50 muM H(2)O(2) in the presence of [U-(13)C]glucose, and cellular and extracellular contents of lactate and glucose were analysed by enzymatic assays and NMR spectroscopy.