Self-protective transcriptional alterations in ZF4 cells exposed to Pb(NO3 )2 and AgNO3

J Biochem Mol Toxicol. 2019 Dec;33(12):e22408. doi: 10.1002/jbt.22408. Epub 2019 Oct 16.

Abstract

In this study, gene expression alterations of phase I to III enzymes, transcription factors, and microRNA (miRNA) in embryonic zebrafish fibroblasts (ZF4) cells after the treatment of Pb(NO3 )2 and AgNO3 were investigated, to illustrate the possible detoxification pathway of heavy metal ions. It was observed that both metals caused concentration-dependent death and moderate elevation of oxidative stress in ZF4 cells. In response to such toxicity, upregulation of multidrug resistance protein (mdr)4 and multiresistance-associated protein (mrp)1 were found. However, enhanced expression of glutathione S-transferase (gst) and cytochrome P450 (cyp)1a could only be detected during the exposure of Pb2+ . In addition, both metals induced extensive upregulation of pregnane X receptor (pxr), but only moderate elevation of E2-related factor (nrf2), while they suppressed the expression of miR-122 and miR-126. In conclusion, Pb2+ and Ag+ shared the same detoxification mechanism including ABC transporters, Pxr, and miRNA in ZF4 cells, which needs further investigation.

Keywords: Ag+; Pb2+; ZF4 cells; detoxification; transcription factors.

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Glutathione Transferase / metabolism
  • Lead / toxicity*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Multidrug Resistance-Associated Proteins / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Nitrates / toxicity*
  • Oxidative Stress / drug effects
  • Pregnane X Receptor / genetics
  • Pregnane X Receptor / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Silver Nitrate / toxicity*
  • Zebrafish / embryology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • MicroRNAs
  • Multidrug Resistance-Associated Proteins
  • NF-E2-Related Factor 2
  • Nitrates
  • Pregnane X Receptor
  • Reactive Oxygen Species
  • Zebrafish Proteins
  • nfe2l2a protein, zebrafish
  • Lead
  • lead nitrate
  • Cytochrome P-450 Enzyme System
  • Silver Nitrate
  • Glutathione Transferase