Oxidative stress is involved in several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic reperfusion injury (stroke). We have established clones of the murine hippocampal neuronal cell line HT22, which are resistant to the oxidative stress-causing agents glutamate and hydrogen peroxide, respectively. These cell clones show a mutual cross-resistance to other oxidative stressors, but not to essentially non-oxidative neurotoxins. We have discovered that the amount of phosphorylated, inactive glycogen synthase kinase (GSK) 3beta is elevated in both resistant clones. Pharmacological inhibition of GSK-3beta with lithium chloride in the sensitive parental neuronal cells results in an increased tolerance to glutamate and hydrogen peroxide, suggesting that GSK-3beta is involved in the control of oxidative stress resistance in these cells.
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