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赭曲霉毒素A诱导HepG-2细胞早期事件的高通量标签测序分析

High-Throughput Tag-Sequencing Analysis of Early Events Induced by Ochratoxin A in HepG-2 Cells.

作者信息

Zhang Yu, Qi Xiaozhe, Zheng Juanjuan, Luo YunBo, Huang Kunlun, Xu Wentao

机构信息

Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, People's Republic of China.

Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University (BTBU), Beijing, 100048, People's Republic of China.

出版信息

J Biochem Mol Toxicol. 2016 Jan;30(1):29-36. doi: 10.1002/jbt.21739. Epub 2015 Sep 17.

Abstract

Ochratoxin A (OTA) is produced by fungi of the species Aspergillus and Penicillium. OTA has displayed hepatotoxicity in mammals. Although recent studies have indicated that OTA influences liver function, little is known regarding its impact on differential early liver toxicity. In this study, we report high-throughput tag-sequencing (Tag-seq) analysis of the transcriptome using Solexa Analyzer platform after 4 h of OTA treatment on HepG-2 cells. The analyses of differentially expressed genes revealed the substantial changes. A total of 21,449 genes were identified and quantified, with 2726 displaying significantly altered expression levels. Expression level data were then integrated with a network of gene-gene interactions, and biological pathways to obtain a systems-level view of changes in the transcriptome that occur with OTA resistance. Our data suggest that OTA exposure leads to an imbalance in zinc finger expression and shed light on splicing factor and mitochondrial-based mechanisms.

摘要

赭曲霉毒素A(OTA)由曲霉属和青霉属真菌产生。OTA在哺乳动物中已表现出肝毒性。尽管最近的研究表明OTA会影响肝功能,但关于其对早期肝脏毒性差异的影响却知之甚少。在本研究中,我们报告了在HepG-2细胞上用OTA处理4小时后,使用Solexa分析仪平台对转录组进行的高通量标签测序(Tag-seq)分析。对差异表达基因的分析揭示了显著变化。总共鉴定并定量了21449个基因,其中2726个显示出表达水平的显著改变。然后将表达水平数据与基因-基因相互作用网络和生物途径整合,以获得对OTA抗性时转录组变化的系统水平视图。我们的数据表明,接触OTA会导致锌指表达失衡,并揭示剪接因子和基于线粒体的机制。

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