Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide
Differential cytotoxic responses of PC12 cells chronically exposed to psychostimulants or to hydrogen peroxide
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DOI：
10.1016/j.tox.2005.08.022
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发表时间：
2006-01-05
期刊：
影响因子：
4.5
通讯作者：
Oliveira, CR
中科院分区：
文献类型：
--
作者：
Cunha-Oliveira, T;Rego, AC;Oliveira, CR
反复滥用可卡因和安非他明等兴奋剂与特定脑区神经元多巴胺蓄积有关。多巴胺可能通过多巴胺氧化代谢产生活性氧物质，即过氧化氢（H2 O2）而具有细胞毒性。在这项工作中，我们研究了在PC 12细胞（多巴胺能神经元模型）慢性和/或急性暴露于可卡因或安非他明的细胞毒性，相比H2 O2暴露。慢性可卡因治疗诱导敏感急性可卡因侮辱和增加可卡因诱发的细胞外多巴胺的积累，虽然没有观察到二羟苯乙酸（DOPAC）水平的变化。此外，多巴胺耗尽细胞慢性暴露于安非他明和急性安非他明毒性持续在这些细胞中，表明多巴胺不参与安非他明的细胞毒性。慢性H2 O2处理的PC 12细胞对急性H2 O2完全耐受，但对急性可卡因或苯丙胺暴露没有耐受性，表明这些刺激性药物诱导的毒性与氧化应激的适应无关。有趣的是，慢性可卡因治疗在很大程度上，但不完全，保护细胞免受H2 O2的挑战，同时观察到细胞内ATP的减少。这项研究表明，慢性治疗的PC 12细胞与可卡因或H2 O2修改细胞毒性反应急性暴露于这些代理。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exposed to cocaine or amphetamine, as compared to H2O2 exposure. Chronic cocaine treatment induced sensitization to acute cocaine insult and increased cocaine-evoked accumulation of extracellular dopamine, although no changes in dihydroxyphenylacetic acid (DOPAC) levels were observed. Moreover, dopamine was depleted in cells chronically exposed to amphetamine and acute amphetamine toxicity persisted in these cells, indicating that dopamine was not involved in amphetamine cytotoxicity. PC12 cells chronically treated with H2O2 were totally resistant to acute H2O2, but not to acute cocaine or amphetamine exposure, suggesting that the toxicity induced by these stimulant drugs is unrelated to adaptation to oxidative stress. Interestingly, chronic cocaine treatment largely, but not completely, protected the cells against a H2O2 challenge, whilst a decrement in intracellular ATP was observed. This study shows that chronic treatment of PC 12 cells with cocaine or H2O2 modifies the cytotoxic response to an acute exposure to these agents. (C) 2005 Elsevier Ireland Ltd. All rights reserved.