BDNF or IGF-I potentiates free radical-mediated injury in cortical cell cultures.
Free radical-mediated damage to cultured cortical neurons was induced by a 24 h exposure to Fe2+ (30 microM) or an inhibitor of gamma-glutamylcysteine synthetase, L-buthionine-[S,R]-sulfoximine (BSO, 1 mM). As expected, neuronal death was blocked by inclusion of the free radical scavenger trolox during the Fe2+ or BSO exposure. However, unexpectedly, pretreatment of the cultures with BDNF or IGF-I markedly potentiated neuronal death. This growth factor-potentiated death was still blocked by trolox, but was insensitive to glutamate antagonists. Concurrent addition of cycloheximide with the growth factors prevented injury potentiation. Present findings suggest that growth factors may increase free radical-induced neuronal death by mechanisms dependent upon protein synthesis.
Gwag
B J
BJ
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Koh
J Y
JY
Chen
M M
MM
Dugan
L L
LL
Behrens
M M
MM
Lobner
D
D
Choi
D W
DW
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D019328:Buthionine Sulfoximine; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000633:toxicity; D005290:Ferric Compounds / Q000633:toxicity; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D007334:Insulin-Like Growth Factor I; D005721:Glutamate-Cysteine Ligase