Hu Tsung-Ming, Chung Hsiang-Sheng, Ping Lieh-Yung, Hsu Shih-Hsin, Tsai Hsin-Yao, Chen Shaw-Ji, Cheng Min-Chih
Department of Psychiatry, Yuli Branch, Taipei Veterans General Hospital, Hualien 98142, Taiwan.
Department of Future Studies and LOHAS Industry, Fo Guang University, Jiaosi, Yilan County 26247, Taiwan.
Brain Sci. 2020 Aug 12;10(8):545. doi: 10.3390/brainsci10080545.
Valproic acid (VPA) is a multifunctional medication used for the treatment of epilepsy, mania associated with bipolar disorder, and migraine. The pharmacological effects of VPA involve a variety of neurotransmitter and cell signaling systems, but the molecular mechanisms underlying its clinical efficacy is to date largely unknown. In this study, we used the isobaric tags for relative and absolute quantitation shotgun proteomic analysis to screen differentially expressed proteins in VPA-treated SH-SY5Y cells. We identified changes in the expression levels of multiple proteins involved in Alzheimer's disease, Parkinson's disease, chromatin remodeling, controlling gene expression via the vitamin D receptor, ribosome biogenesis, ubiquitin-mediated proteolysis, and the mitochondrial oxidative phosphorylation and electron transport chain. Our data indicate that VPA may modulate the differential expression of proteins involved in mitochondrial function and vitamin D receptor-mediated chromatin transcriptional regulation and proteins implicated in the pathogenesis of neurodegenerative diseases.
丙戊酸（VPA）是一种多功能药物，用于治疗癫痫、双相情感障碍相关的躁狂症和偏头痛。VPA的药理作用涉及多种神经递质和细胞信号系统，但其临床疗效背后的分子机制迄今仍 largely未知。在本研究中，我们使用等压标签相对和绝对定量鸟枪法蛋白质组学分析来筛选VPA处理的SH-SY5Y细胞中差异表达的蛋白质。我们鉴定出参与阿尔茨海默病、帕金森病、染色质重塑、通过维生素D受体控制基因表达、核糖体生物发生、泛素介导的蛋白水解以及线粒体氧化磷酸化和电子传递链的多种蛋白质的表达水平发生了变化。我们的数据表明，VPA可能调节参与线粒体功能和维生素D受体介导的染色质转录调控的蛋白质以及与神经退行性疾病发病机制相关的蛋白质的差异表达。
