Neurotrophic factor effects on oxidative stress-induced neuronal death.
Neurotrophic factors have been shown to potentiate necrotic neuronal death in cortical cultures. In this study we characterized the death induced by various oxidative insults and tested the effects of neurotrophic factors on that death. Treatment with fibroblast growth factor-2, neurotrophin-4, or insulin-like growth factor-1 potentiated neuronal cell death induced by iron-citrate (Fe) or buthionine sulfoximine (BSO), but not ethacrynic acid (EA). Neuronal death induced by each insult was blocked by the free radical scavenger, trolox. An analysis of the death indicated that Fe and BSO induced necrotic cell death, while EA induced apoptotic cell death. BSO and EA caused decreased cellular glutathione levels, whereas Fe had no effect on glutathione levels. Neurotrophic factors had no effect on the changes in glutathione. The results indicate that oxidative insults can induce either apoptotic or necrotic death and that the effects of neurotrophic factors are dependent on the type of cell death.
Lobner
Doug
D
Department of Biomedical Sciences and Integrative Neuroscience Research Center, Marquette University, Milwaukee, Wisconsin 53233, USA. Doug.Lobner@marquette.edu
Golner
Susan
S
Hjelmhaug
Julie
J
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002839:Chromans / Q000494:pharmacology; D019343:Citric Acid; D004976:Ethacrynic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
D002839:Chromans; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D019343:Citric Acid; C016600:ferrous citrate; D019328:Buthionine Sulfoximine; D007334:Insulin-Like Growth Factor I; D004976:Ethacrynic Acid; C073922:neurotrophin 4; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid