An integrated study of acute effects of valproic acid in the liver using metabonomics, proteomics, and transcriptomics platforms
An integrated study of acute effects of valproic acid in the liver using metabonomics, proteomics, and transcriptomics platforms
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DOI：
10.1089/omi.2006.10.1
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发表时间：
2006-03-01
影响因子：
3.3
通讯作者：
Dragan, Yvonne P.
中科院分区：
文献类型：
--
作者：
Schnackenberg, Laura K.;Jones, Richard C.;Dragan, Yvonne P.
为了阐明丙戊酸（VPA）急性肝毒性的系统生物学水平的理解，采用了综合组学方法。本系统生物学研究采用了代谢组学、蛋白质组学和基因表达微阵列平台。分别皮下注射600 mg/kg VPA和对照剂。在给药后6、12和24小时收集尿液、血清和肝组织。代谢组学数据的主成分分析（PCA）显示给药组的聚类远离尿液样本的对照组。在调查的其他样本集中可以看到松散的聚类。然而，VPA给药后12和24小时尿液样本以及12小时肝组织水提取物中葡萄糖浓度发生改变。蛋白质组学研究发现两种蛋白质，糖原磷酸化酶和淀粉-1,6-葡萄糖苷酶，在给药的动物中相对于对照组增加。这两种蛋白质都参与将糖原转化为葡萄糖。在VPA暴露后6、12或24小时，检查20,000个肝脏基因的表达并没有发现显著的表达改变。综合研究表明，服用VPA后糖原溶解途径受到干扰。
An integrated omics approach was undertaken in order to elucidate a systems biology level understanding of the acute hepatotoxcity of valproic acid (VPA). Metabonomics, proteomics and gene expression microarray platforms were employed in this systems biology study. CD-1 female pregnant mice were injected subcutaneously with 600 mg/kg VPA or vehicle control. Urine, serum, and liver tissue were collected at 6, 12, and 24 h after dosing. Principal component analysis (PCA) of the metabonomics data showed clustering of the dosed groups away from the controls for the urine samples. Looser clustering was seen in the other sample sets investigated. However, VPA administration resulted in altered glucose concentrations in urine samples at 12 and 24 h and in aqueous liver tissue extracts at 12 h after VPA administration. Proteomics studies identified two proteins, glycogen phosphorylase and amylo-1,6-glucosidase, which were increased in dosed animals relative to control. Both of these proteins are involved in converting glycogen to glucose. Examination of the expression of 20,000 liver genes did not reveal significantly altered expression at 6, 12, or 24 h after VPA exposure. The combined studies indicated a perturbation in the glycogenolysis pathway following administration of VPA.