Neurotoxicity of free-radical-mediated serotonin neurotoxin in cultured embryonic chick brain neurons.
Neurotoxicity of free-radical-mediated serotonin neurotoxin in cultured embryonic chick brain neurons.
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自由基介导的血清素神经毒素对培养的胚胎鸡脑神经元的神经毒性。
DOI：
10.1016/0014-2999(96)00059-3
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发表时间：
1996
影响因子：
5
通讯作者：
Volicer,L
中科院分区：
文献类型：
--
作者：
Chen,JC;Fine,RE;Squicciarini,J;Volicer,L
5-羟色胺（5-HT）暴露于氧衍生的自由基生成系统、黄嘌呤氧化酶-次黄嘌呤或芬顿反应导致神经毒素色胺-4，5-二酮的形成。在培养的鸡胚脑神经元中，色胺-4，5-二酮或其碳酸乙酯衍生物的孵育导致剂量依赖性神经毒性（1-100 μM）。巯基化合物谷胱甘肽（2 μ M或10 μM）的加入显著增强了10 μM色胺-4，5-二酮的毒性。相反，10 μM谷胱甘肽可降低10 μM 5，6-和5，7-二羟色胺对培养神经元的神经毒性作用。5-HT摄取抑制剂氟西汀可完全预防5，6-和5，7-二羟色胺的毒性。然而，色胺-4，5-二酮和谷胱甘肽结合物引起的毒性不能被氟西汀（10或100 μM）或谷胱甘肽转移酶抑制剂硼酸/丝氨酸阻断。结果表明，不同的5-HT衍生的神经毒素的分子机制，并建议色胺-4，5-二酮和/或其谷胱甘肽共轭物会导致神经元损伤，如果它们在体内形成。
Exposure of serotonin (5-HT) to oxygen-derived free-radical-generating system, xanthine oxidase-hypoxanthine or to a Fenton reaction results in the formation of the neurotoxin, tryptamine-4,5-dione. In cultured embryonic chick brain neurons, incubation of tryptamine-4,5-dione or its ethyl carbonate derivative resulted in a dose-dependent neurotoxicity (1–100 μM). The addition of sulfhydryl compound, glutathione at 2 or 10 μM significantly enhanced the toxicity induced by 10 μM tryptamine-4,5-dione. On the contrary, glutathione at 10 μM decreased the neurotoxic effect caused by 10 μM 5,6- and 5,7-dihydroxytryptamine in the cultured neurons. The toxicity resulted from 5,6- and 5,7-dihydroxytryptamine could be fully prevented by a 5-HT uptake inhibitor, fluoxetine. However, the toxicity caused by tryptamine-4,5-dione and glutathione conjugate could not be blocked by fluoxetine (10 or 100 μM) or by a glutathione transferase inhibitor, boric acid/serine. The results indicate a different molecular mechanism among 5-HT derived neurotoxins and suggest that tryptamine-4,5-dione and/or its glutathione conjugate would cause neuronal damage, if they are formed in vivo.