Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in rainbow trout (Oncorhynchus mykiss)

Aquat Toxicol. 2004 Aug 25;69(3):271-80. doi: 10.1016/j.aquatox.2004.06.002.


Rainbow trout (Oncorhynchus mykiss) were exposed to 1.65 microM of waterborne copper for 24 h. Fish were then transferred to metal-free water. Metallothionein mRNA induction in rainbow trout liver and gill tissue, hypoxia-inducible factor-1 (HIF-1alpha) accumulation in gill tissue and arithmetic mean thickness of gill epithelium (Har) were determined at 4 and 24h of exposure as well as 48 h after transfer to metal-free water. The arithmetic mean distance from water to blood was significantly elevated after both 4 and 24 h of exposure (Har was 4.67 and 4.66 microm, respectively in exposed fish, compared to 3.81 and 3.62 microm for the corresponding control fish). During the 48 h recovery Har returned towards the control values; the recovery value of 4.21 microm was significantly lower than values during exposures. There was also a significant increase in gill metallothionein mRNA levels after the 4 h exposure with MT/GAPDH ratio of 1.288 versus the control value of 0.988. In liver, metallothionein induction was not observed. HIF-1alpha protein showed an increased accumulation in gills after 4 h, with the HIF-1alpha/alpha-tubulin ratio of 0.562 being significantly higher than the 24 h exposure value of 0.232. These results suggest that exposure to copper for four hours causes hypoxia in the gill epithelium, which is adequate for the activation of HIF-1alpha.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Body Weights and Measures
  • Copper / toxicity*
  • Gills / drug effects*
  • Gills / metabolism
  • Gills / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Liver / drug effects
  • Liver / metabolism
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Oncorhynchus mykiss / metabolism*
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Toxicity Tests, Acute
  • Transcription Factors / metabolism*


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Transcription Factors
  • Copper
  • Metallothionein