Wolters JarnoEJ, van Breda SimoneGJ, Claessen SandraM, de Kok TheoMCM, Kleinjans JosCS
Department of Toxicogenomics, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Data Brief. 2017 Nov 10;16:161-171. doi: 10.1016/j.dib.2017.11.031. eCollection 2018 Feb.
Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis. However the exact mechanism of the steatosis formation is unknown. The data presented in this DIB publication is used to further investigate the VPA-induced mechanisms of steatosis by analyzing changes in patterns of methylation. Therefore, primary human hepatocytes (PHHs) were exposed to VPA at a concentration which was shown to cause steatosis without inducing overt cytotoxicity. VPA was administered for 5 days daily to PHHs. Furthermore, after 5 days VPA-treatment parts of the PHHs were followed for a 3 days washout. Differentially methylated DNA regions (DMRs) were identified by using the 'Methylated DNA Immuno-Precipitation - sequencing' (MeDIP-seq) method. The data presented in this DIB demonstrate induced steatosis pathways by all DMRs during VPA-treatment, covering interesting drug-induced steatosis genes (persistent DMRs upon terminating VPA treatment and the network). This was illustrated in our associated article (Wolters et al., 2017) [1]. MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).
丙戊酸(VPA)是一种在全球广泛使用的抗癫痫药物。尽管其具有重要的药理学意义,但它可能会导致肝毒性和脂肪变性。然而,脂肪变性形成的确切机制尚不清楚。本DIB出版物中呈现的数据用于通过分析甲基化模式的变化来进一步研究VPA诱导的脂肪变性机制。因此,将原代人肝细胞(PHHs)暴露于已证明会导致脂肪变性但不诱导明显细胞毒性的浓度的VPA中。每天给PHHs施用VPA,持续5天。此外,在VPA处理5天后,对部分PHHs进行3天的洗脱期观察。通过使用“甲基化DNA免疫沉淀-测序”(MeDIP-seq)方法鉴定差异甲基化DNA区域(DMRs)。本DIB中呈现的数据表明,在VPA处理期间,所有DMRs均诱导了脂肪变性途径,涵盖了有趣的药物诱导脂肪变性基因(VPA处理终止后持续存在的DMRs及其网络)。这在我们的相关文章(Wolters等人,2017年)[1]中得到了说明。MeDIP-seq原始数据可在ArrayExpress上获取(登录号:E-MTAB-4437)。