Transcription alterations of microRNAs, cytochrome P4501A1 and 3A65, and AhR and PXR in the liver of zebrafish exposed to crude microcystins

Toxicon. 2013 Oct:73:17-22. doi: 10.1016/j.toxicon.2013.07.002. Epub 2013 Jul 12.

Abstract

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.

Keywords: Cytochrome P450; MicroRNA; Microcystins; Transcription; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP1A1 / metabolism*
  • DNA Primers / genetics
  • Gene Expression Regulation / drug effects*
  • Liver / metabolism*
  • MicroRNAs / metabolism
  • Microcystins / toxicity*
  • Oxidoreductases, N-Demethylating / metabolism
  • Pregnane X Receptor
  • Real-Time Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon / metabolism
  • Receptors, Steroid / metabolism
  • Zebrafish
  • Zebrafish Proteins / metabolism

Substances

  • DNA Primers
  • MIRN122 microRNA, zebrafish
  • MIRN21 microRNA, zebrafish
  • MicroRNAs
  • Microcystins
  • Pregnane X Receptor
  • Receptors, Aryl Hydrocarbon
  • Receptors, Steroid
  • Zebrafish Proteins
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A1
  • cytochrome P-450 CYP3A65, zebrafish
  • Oxidoreductases, N-Demethylating