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首页> 外文期刊>The European Journal of Neuroscience >Valproate robustly increases Sp transcription factor-mediated expression of the dopamine transporter gene within dopamine cells.
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Valproate robustly increases Sp transcription factor-mediated expression of the dopamine transporter gene within dopamine cells.

机译：丙戊酸盐在多巴胺细胞内强烈增加Sp转录因子介导的多巴胺转运蛋白基因的表达。

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摘要

Several lines of evidence suggest that valproate, a drug used in the treatment of mania and bipolar disorders, epilepsies, and addictions, may modulate dopamine transporter (DAT) function, yet the effects of valproate on DAT gene expression have not been directly assessed. Utilizing a human dopaminergic cell line and rat midbrain dopamine (DA) neurons in organotypic culture, we found that valproate increased endogenous DAT gene expression in a concentration- and time-dependent manner. Given previous data demonstrating that members of the specificity protein (Sp) family of transcription factors are strong trans-activators of DAT gene transcription, we investigated the Sp-dependence of valproate effects. Valproate-induced transcription of a DAT reporter construct was significantly attenuated by coexpression of a dominant negative form of Sp, mutation of a Sp-responsive cis-element, or expression in a Sp-null cellular background (SL-2 cells). Valproate significantly altered Sp protein abundance in both dopaminergic model systems employed. In summary, valproate treatment significantly increased DAT gene expression in a Sp transcription factor-dependent manner. Some of valproate's therapeutic effects may involve activation of DAT gene expression.
机译：有几条证据表明，丙戊酸盐（一种用于治疗躁狂症和双相情感障碍，癫痫和成瘾的药物）可能会调节多巴胺转运蛋白（DAT）的功能，但尚未直接评估丙戊酸盐对DAT基因表达的影响。利用人类多巴胺能细胞系和大鼠中脑多巴胺（DA）神经元的器官型培养，我们发现丙戊酸盐以浓度和时间依赖性方式增加内源性DAT基因表达。鉴于先前的数据表明特异性蛋白质（Sp）转录因子家族的成员是DAT基因转录的强反式激活因子，我们研究了丙戊酸盐作用的Sp依赖性。丙戊酸诱导的DAT报告基因构建体的转录通过Sp的显性阴性形式的共表达，Sp响应的顺式元件的突变或Sp空细胞背景（SL-2细胞）中的表达而显着减弱。在使用的两种多巴胺能模型系统中，丙戊酸盐均显着改变了Sp蛋白的丰度。总之，丙戊酸治疗以Sp转录因子依赖性方式显着增加DAT基因表达。丙戊酸盐的某些治疗作用可能涉及DAT基因表达的激活。

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