College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
Toxicon. 2013 Oct;73:17-22. doi: 10.1016/j.toxicon.2013.07.002. Epub 2013 Jul 12.
MicroRNAs are small non-coding regulatory RNAs that not only control diverse cellular processes but also regulate gene expression induced by environmental chemicals. However, little is known about the role of microRNAs in liver response of fish to the exposure of cyanobacterial hepatotoxin microcystins (MCs). In the present study, the transcription levels of 4 miRNAs (dre-miR-21, dre-miR-122, dre-miR-27b, and dre-miR-148), cytochromes P450s CYP1A1 and CYP3A65, and their receptors, aryl hydrocarbon receptor (AhR, for CYP1A1) and pregnane X receptor (PXR, for CYP3A65), in the liver of zebrafish were evaluated after 24 h of 50, 200, or 800 μg/L of crude MCs exposure by using the quantitative real-time PCR method. The results showed that MCs-exposure elevated the transcription levels of dre-miR-21 and dre-miR-27b while down-regulated the expressions of dre-miR-122 and dre-miR-148. However, CYP1A1 transcription remained unchanged while mRNA levels of AhRR1 and AhR2 were significantly higher than that of control. Furthermore, the expressions of CYP3A65 and its receptor PXR were up-regulated by MCs-exposure at higher concentrations (200, or 800 μg/L of crude MCs). Therefore we suggest that CYP3A65 and PXR may be involved in the metabolization and detoxification of MCs in zebrafish, which may be regulated by dre-miR-27b. This work might be beneficial for the discovery of new potential diagnostic biomarker and drug target for hepatosis caused by MC.
微小 RNA 是一类小型非编码调控 RNA，不仅可以控制多种细胞过程，还可以调节环境化学物质诱导的基因表达。然而，人们对微小 RNA 在鱼类肝脏对蓝藻肝毒素微囊藻毒素（MCs）暴露的反应中的作用知之甚少。在本研究中，通过定量实时 PCR 方法，评估了 4 种微小 RNA（dre-miR-21、dre-miR-122、dre-miR-27b 和 dre-miR-148）、细胞色素 P450s CYP1A1 和 CYP3A65 及其受体芳烃受体（AhR，用于 CYP1A1）和孕烷 X 受体（PXR，用于 CYP3A65）在斑马鱼肝脏中的转录水平，暴露于 50、200 或 800μg/L 粗制 MCs 24 小时后。结果表明，MCs 暴露升高了 dre-miR-21 和 dre-miR-27b 的转录水平，而降低了 dre-miR-122 和 dre-miR-148 的表达。然而，CYP1A1 转录保持不变，而 AhRR1 和 AhR2 的 mRNA 水平明显高于对照。此外，在较高浓度（200 或 800μg/L 粗制 MCs）下，CYP3A65 及其受体 PXR 的表达上调。因此，我们认为 CYP3A65 和 PXR 可能参与了 MCs 在斑马鱼中的代谢和解毒，这可能受到 dre-miR-27b 的调节。这项工作可能有助于发现新的潜在诊断生物标志物和药物靶点，用于治疗由 MC 引起的肝损伤。
