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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells.
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Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells.

机译:典型(氟哌啶醇)和非典型(利培酮)抗精神病药对大鼠神经干细胞蛋白质表达的影响。

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摘要

Neural stem cells (NSCs) play a crucial role in the development and maturation of the central nervous system. Recently studies suggest that antipsychotic drugs regulate the activities of NSCs. However, the molecular mechanisms underlying antipsychotic-induced changes of the activity of NSCs, particularly protein expression, are still unknown. We studied the growth and protein expression in haloperidol (HD) and risperidone (RS) treated rat NSCs. The treatment with RS (3microM) or HD (3microM) had no effect on morphology of NSCs after 24h, but significantly promotes or inhibits the differentiation of NSCs after a 96h of treatment. 2-DE based proteomics was performed at 24h, a stage before phenotypic expression of NSCs. Gel image analysis revealed that 30 protein spots in HD- and 60 spots in RS-treated groups were differentially regulated in their expression compared to control group (p<0.05; ANOVA). When these spots were compared between the two drug-treated groups, 23 spots overlapped leaving 7 HD-specific and 37 RS-specific spots. Of these 67 spots, 32 different proteins were identified. The majority of the differentially regulated proteins were classified into several functional groups, such as cytoskeletal, calcium regulating protein, metabolism, signal transduction and proteins related to oxidative stress. Our data shows that atypical RS expressed more proteins than typical HD, and these results might explain the molecular mechanisms underlying the different effects of both drugs on NSCs activities as described above. Identified proteins in this experiment may be useful in future studies of NSCs differentiation and/or understanding in molecular mechanisms of different neural diseases including schizophenia.
机译:神经干细胞(NSC)在中枢神经系统的发育和成熟中起着至关重要的作用。最近的研究表明,抗精神病药可调节NSC的活性。但是,尚不清楚抗精神病药诱导的NSC活性(尤其是蛋白质表达)变化的分子机制。我们研究了氟哌啶醇(HD)和利培酮(RS)处理的大鼠NSC的生长和蛋白质表达。 RS(3microM)或HD(3microM)处理在24小时后对NSC的形态没有影响,但在处理96小时后显着促进或抑制了NSC的分化。在NSC表型表达之前的24小时进行基于2-DE的蛋白质组学。凝胶图像分析显示,与对照组相比,HD处理组中的30个蛋白点和RS处理组中的60个蛋白点在表达上受到差异性调节(p <0.05; ANOVA)。在两个药物治疗组之间比较这些斑点时,有23个斑点重叠,剩下7个HD特异性斑点和37个RS特异性斑点。在这67个斑点中,鉴定出32种不同的蛋白质。大多数差异调节蛋白被分为几个功能组,例如细胞骨架,钙调节蛋白,代谢,信号转导和与氧化应激有关的蛋白。我们的数据表明,非典型RS比典型的HD表达更多的蛋白质,这些结果可能解释了上述两种药物对NSC活性不同作用的分子机制。在此实验中鉴定的蛋白质可能对NSC分化的进一步研究和/或理解包括精神分裂症在内的不同神经疾病的分子机制可能有用。

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