Nitrite-induced hepatotoxicity in Bluntsnout bream (Megalobrama amblycephala): the mechanistic insight from transcriptome to physiology analysis

Environ Toxicol Pharmacol. 2014 Jan;37(1):55-65. doi: 10.1016/j.etap.2013.11.010. Epub 2013 Nov 19.

Abstract

Previous studies have investigated the physiological responses to acute nitrite exposure in fish; however, little information is available for the underlying molecular mechanisms of nitrite toxicity in aquatic ecosystems. In an effort to understand the underlying mechanisms of nitrite tolerance and to illuminate global gene expression patterns modulated by nitrite toxicity, we sampled livers from juvenile Megalobrama amblycephala exposed in 0.1, 15 and 30 mg L(-1) nitrite and performed short read (100 bp) next generation RNA sequencing (RNA-seq). The RNA-seq reads from all the exposures (≈24 million reads) were assembled into unigenes datasets according to an available reference transcriptome. Using reads from each nitrite concentration, we performed RNA-seq based gene expression analysis that identified a total of 357 differentially expressed genes. The differentially expressed genes were related to oxidative stress, apoptotic pathway, oxygen transport, immune responses and the metabolism of proteins and fats. Quantitative real-time polymerase chain reaction using six genes independently verified the RNA-seq results, the present study suggests several new candidate genes commonly regulated in liver of M. amblycephala. In addition to liver histology examinations, this study provides important mechanistic insights into nitrite-induced liver toxicity in a whole-animal physiology context, which will help in understanding the syndromes caused by nitrite poisoning.

Keywords: Antioxidant enzyme; Liver; Megalobrama amblycephala; Nitrite; Physiology; Transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyprinidae / genetics*
  • Fish Proteins / genetics*
  • Gene Expression Profiling
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver / ultrastructure
  • Microscopy, Electron, Transmission
  • Nitrites / toxicity*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Water Pollutants, Chemical / toxicity*

Substances

  • Fish Proteins
  • Nitrites
  • RNA, Messenger
  • Water Pollutants, Chemical