Gwag B J, Koh J Y, Chen M M, Dugan L L, Behrens M M, Lobner D, Choi D W
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Neuroreport. 1995 Dec 29;7(1):93-6.
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.
通过将培养的皮层神经元暴露于Fe2+（30微摩尔）24小时或γ-谷氨酰半胱氨酸合成酶抑制剂L-丁硫氨酸-[S,R]-亚砜亚胺（BSO，1毫摩尔）来诱导自由基介导的损伤。正如预期的那样，在暴露于Fe2+或BSO期间，通过加入自由基清除剂生育三烯酚可阻止神经元死亡。然而，出乎意料的是，用脑源性神经营养因子（BDNF）或胰岛素样生长因子-I（IGF-I）对培养物进行预处理可显著增强神经元死亡。这种生长因子增强的死亡仍可被生育三烯酚阻断，但对谷氨酸拮抗剂不敏感。将环己酰亚胺与生长因子同时添加可防止损伤增强。目前的研究结果表明，生长因子可能通过依赖蛋白质合成的机制增加自由基诱导的神经元死亡。
