Inhibition of protein phosphatases impairs the ability of astrocytes to detoxify hydrogen peroxide.

摘要: We have used protein phosphatase (PP) inhibitors and rat cerebellar glial cells in primary culture to investigate the role of PP activity ability detoxify exogenously applied hydrogen peroxide (H2O2). The marine toxin okadaic acid (OKA), a potent PP1 PP2A inhibitor, caused concentration-dependent degeneration astrocytes increased formation hydroperoxide radicals significantly. Subtoxic exposures OKA significantly potentiated toxicity by exogenous H2O2. concentration H2O2 that reduced 50% survival after 3 h was estimated at 720+/-40 microM absence 85+/-30 presence toxin. calyculin A endothall also astrocytes. time-dependent inhibition both catalase glutathione peroxidase, reducing approximately these enzymes h, whereas other enzymatic activities remained unaffected. Also, cellular content total elevated oxidized about 25% glutathione. OKA-treated cleared from incubation medium two times more slowly than control cultures. Our results suggest prominent for antioxidant mechanisms protecting against damage