Pleiotrophin prevents cocaine-induced toxicity in vitro
Pleiotrophin prevents cocaine-induced toxicity in vitro
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DOI：
10.1016/j.ejphar.2008.07.067
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发表时间：
2008-10-24
影响因子：
5
通讯作者：
Herradon, Gonzalo
中科院分区：
文献类型：
--
作者：
Gramage, Esther;Alguacil, Luis F.;Herradon, Gonzalo
Pleiotroin是一种参与中枢神经系统分化、存活和修复过程的细胞因子。在给予不同的药物滥用后，Pleiotroin在大脑中表达上调，因此表明这种细胞因子对药物诱导的毒性具有保护作用。我们已经用NG108-15细胞在体外验证了这一假设，NG108-15细胞被广泛用于神经毒性研究。通过中性红试验发现，多效营养素(下午3点和6点)可显著抑制可卡因(5 MM)诱导的细胞毒性。在PC12细胞中也得到了类似的结果，发现内源性表达多营养素及其主要靶点受体蛋白酪氨酸磷酸酶(RPTP)β/Zeta。用抗多营养素抗体(2微克/毫升)阻断多营养素信号通路并不能增强可卡因诱导的毒性；有趣的是，仅与抗多营养素抗体共同孵育PC12细胞可显著降低细胞存活率，因此提示内源性多营养素信号在细胞存活中起重要作用。这些数据表明，药物滥用后多效营养素的过度表达可能与预防药物毒性有关。(C)2008爱思唯尔B.V.保留所有权利。
Pleiotrophin is a cytokine involved in differentiation, survival and repair processes in the central nervous system. Pleiotrophin is upregulated in the brain after administration of different drugs of abuse, thus suggesting a protective role of this cytokine on drug-induced toxicity. We have tested this hypothesis in vitro using NG108-15 cells, a line widely used for neurotoxicity studies. It was found that pleiotrophin (3 and 6 pm) significantly prevents cocaine (5 mM)-induced cytotoxicity as measured by the neutral red test. Similar results were obtained in PC12 cells, which were found to endogenously express both pleiotrophin and its main target, receptor protein tyrosine phosphatase (RPTP) beta/zeta. Blockade of pleiotrophin signaling using anti-pleiotrophin antibodies (2 mu g/ml) did not potentiate cocaine-induced toxicity; interestingly, incubation of PC12 cells only with anti-pleiotrophin antibodies significantly reduced cellular viability, thus suggesting an important role of endogenous pleiotrophin signaling in cell survival. The data suggest that pleiotrophin overexpression in response to drugs of abuse may be relevant to prevent drug-induced toxicity. (C) 2008 Elsevier B.V. All rights reserved.