Chlorpromazine inhibits mitochondrial apoptotic pathway via increasing expression of tissue factor
Chlorpromazine inhibits mitochondrial apoptotic pathway via increasing expression of tissue factor
复制标题
氯丙嗪通过增加组织因子表达抑制线粒体凋亡途径
DOI：
10.1016/j.biocel.2015.11.008
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发表时间：
2016
影响因子：
4
通讯作者：
Zhang Fengmin
中科院分区：
文献类型：
--
作者：
Wu Jing;Li Aimei;Li Yujun;Li Xiaoguang;Zhang Qingmeng;Song Wuqi;Wang Yao;Ogutu James O.;Wang Jindong;Li Jianbo;Tang Renkuan;Zhang Fengmin
氯丙嗪（Chlorpromazine， CPZ）是一种广泛应用的抗精神病药物，对多巴胺受体具有拮抗作用。越来越多的证据表明，CPZ在多种毒性和凋亡模型中起神经保护作用。然而，产生这种保护作用的潜在机制尚不清楚。在此，我们评估CPZ对神经元系统线粒体凋亡通路的影响。与未服用抗精神病药物的对照组相比，cpz治疗的精神分裂症患者海马中b细胞淋巴瘤-2 （Bcl-2）和组织因子（TF）水平较高，而凋亡率较低。此外，CPZ短期和长期治疗大鼠均可上调Bcl-2和TF水平，但无细胞毒性作用。体外实验中，转染pEGFP-N1-TF重组质粒后，Bcl-2在C6胶质瘤细胞中的表达上调。此外，在另一个独立的大鼠凋亡模型中，与仅给醇组相比，cpz预处理的大鼠大脑中cleaved caspase-3、细胞色素c和Bax的表达较低，但Bcl-2和TF的表达较高。我们的数据表明，CPZ通过上调TF表达抑制线粒体凋亡通路的激活来发挥神经元保护作用，从而为CPZ的功能和应用提供了新的认识。
Chlorpromazine (CPZ) is a widely used antipsychotic drug with antagonistic effect on dopamine receptors. Accumulating evidence has shown that CPZ plays a neuroprotective role in various models of toxicity and apoptosis. However, the underlying mechanism contributing to this protective effect remains unclear. Here, we evaluate the effect of CPZ on mitochondrial apoptotic pathway in the neuron system. Higher levels of B-cell lymphoma-2 (Bcl-2) and tissue factor (TF) but lower apoptotic rate were found in hippocampus of CPZ-treated schizophrenic patients compared with non-antipsychotic treated controls. Additionally, both short-term and long-term treatment of CPZ in rats could up-regulate the levels of Bcl-2 and TF with no cytotoxic effects. In the in vitro experiment, expression of Bcl-2 was up-regulated in the C6 glioma cells transfected with pEGFP-N1-TF recombinant plasmid. Furthermore, in another independent rat model of apoptosis, compared with the group administrated with alcohol only, the brains of the CPZ-pretreated rats showed lower expression of cleaved caspase-3, cytochrome c and Bax, but higher expression of Bcl-2 and TF. Our data demonstrate that CPZ exerts its neuronal protective effects through inhibiting the activation of mitochondrial apoptotic pathway by up-regulating TF expression, thus providing new insight into CPZ function and application.