Inhibition of glycogen synthase kinase 3 beta is involved in the resistance to oxidative stress in neuronal HT22 cells.
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.
Schäfer
Monika
M
Independent Research Group Neurodegeneration, Max Planck Institute for Psychiatry, Munich, Germany.
Goodenough
Sharon
S
Moosmann
Bernd
B
Behl
Christian
C
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride