Identification of biochemical and cytotoxic markers in cocaine treated PC12 cells.
Identification of biochemical and cytotoxic markers in cocaine treated PC12 cells.
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DOI：
10.1038/s41598-018-21182-7
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发表时间：
2018-02-09
影响因子：
4.6
通讯作者：
Goodman CB
中科院分区：
文献类型：
--
作者：
Badisa RB;Batton CS;Mazzio E;Grant SC;Goodman CB
可卡因是一种强大的成瘾性药物，在大多数西方国家被广泛滥用。由于高亲脂性，可卡因容易到达中枢神经系统（CNS）的各个领域，并引发不同水平的细胞毒性。本研究的目的是通过对生化和细胞毒性标志物的定量了解，在分化的PC 12细胞中重现可卡因毒性。我们用0.1 μg/ml的神经生长因子（NGF）诱导细胞分化5天，然后用体内和体外浓度的可卡因处理48小时。结果表明，可卡因在体内浓度既不杀死细胞，也不改变形态，但降低线粒体膜电位，增加乳酸和谷胱甘肽（GSH）水平。另一方面，可卡因在体外浓度损伤神经突，并导致细胞死亡，这对应于增加活性氧（ROS）的产生，质膜损伤，GSH耗尽，没有检测到一氧化氮（NO）水平。虽然直接了解可卡因和细胞在体内动物模型下的相互作用是由于高复杂性阻碍，我们目前在体外的结果有助于了解可卡因治疗的神经元细胞神经退行性疾病的一些关键事件的发作。
Cocaine is one of the powerful addictive drugs, widely abused in most Western countries. Because of high lipophilic nature, cocaine easily reaches various domains of the central nervous system (CNS) and triggers different levels of cellular toxicity. The aim of this investigation was to reproduce cocaine toxicity in differentiated PC12 cells through quantitative knowledge on biochemical and cytotoxicity markers. We differentiated the cells with 0.1 μg/ml nerve growth factor (NGF) for 5 days, followed by treatment with cocaine for 48 h at in vivo and in vitro concentrations. Results indicated that cocaine at in vivo concentrations neither killed the cells nor altered the morphology, but decreased the mitochondrial membrane potential that paralleled with increased lactate and glutathione (GSH) levels. On the other hand, cocaine at in vitro concentrations damaged the neurites and caused cell death, which corresponded with increased reactive oxygen species (ROS) generation, plasma membrane damage, and GSH depletion with no detectable nitric oxide (NO) level. While direct understanding of cocaine and cell interaction under in vivo animal models is impeded due to high complexity, our present in vitro results assisted in understanding the onset of some key events of neurodegenerative diseases in cocaine treated neuronal cells.
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影响因子：
5.4
作者：
Badisa, Ramesh B.;Goodman, Carl B.;Fitch-Pye, Cheryl A.
通讯作者：
Fitch-Pye, Cheryl A.
影响因子：
158.5
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
Gramage, Esther;Alguacil, Luis F.;Herradon, Gonzalo
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