Inhibition of protein phosphatases impairs the ability of astrocytes to detoxify hydrogen peroxide
| Autor: | Amaia Ferrero-Gutiérrez, M. Teresa Fernández-Sánchez, Anabel Pérez-Gómez, Antonello Novelli |
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| Rok vydání: | 2007 |
| Předmět: |
Antioxidant
Free Radicals medicine.medical_treatment Phosphatase medicine.disease_cause Biochemistry chemistry.chemical_compound Physiology (medical) Cerebellum Hexokinase Okadaic Acid medicine Phosphoprotein Phosphatases Animals Hydrogen peroxide Cells Cultured chemistry.chemical_classification biology Superoxide Dismutase Glutathione peroxidase Glucose-6-Phosphate Isomerase Okadaic acid Hydrogen Peroxide Catalase Molecular biology Glutathione Rats Enzyme Activation Oxidative Stress chemistry Astrocytes biology.protein Marine toxin Oxidative stress |
| Zdroj: | Free radical biologymedicine. 44(10) |
| ISSN: | 0891-5849 |
| Popis: | We have used protein phosphatase (PP) inhibitors and rat cerebellar glial cells in primary culture to investigate the role of PP activity in the ability of glial cells to detoxify exogenously applied hydrogen peroxide (H2O2). The marine toxin okadaic acid (OKA), a potent PP1 and PP2A inhibitor, caused a concentration-dependent degeneration of astrocytes and increased the formation of hydroperoxide radicals significantly. Subtoxic exposures to OKA significantly potentiated toxicity by exogenous H2O2. The concentration of H2O2 that reduced by 50% the survival of astrocytes after 3 h was estimated at 720+/-40 microM in the absence and 85+/-30 microM in the presence of the toxin. The PP inhibitors calyculin A and endothall also potentiated H2O2 toxicity in cerebellar astrocytes. OKA caused a time-dependent inhibition of both glial catalase and glutathione peroxidase, reducing by approximately 50% the activity of these enzymes after 3 h, whereas other enzymatic activities remained unaffected. Also, OKA reduced the cellular content of total glutathione and elevated oxidized glutathione to about 25% of total glutathione. OKA-treated astrocytes cleared H2O2 from the incubation medium approximately two times more slowly than control cultures. Our results suggest a prominent role for PP activity in the antioxidant mechanisms protecting astrocytes against damage by H2O2. |
| Databáze: | OpenAIRE |
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