PUBLICATION

Hypoxia suppressed copper toxicity during early development in zebrafish embryos in a process mediated by the activation of the HIF signalling pathway

Authors
Fitzgerald, J.A., Jameson, H.M., Dewar Fowler, V.H., Bond, G.L., Bickley, L.K., Uren Webster, T.M., Bury, N.R., Wilson, R.J., Santos, E.M.
ID
ZDB-PUB-160329-2
Date
2016
Source
Environmental science & technology   50(8): 4502-12 (Journal)
Registered Authors
Bury, Nicolas, Santos, Eduarda
Keywords
none
MeSH Terms
  • Amino Acids, Dicarboxylic/pharmacology
  • Animals
  • Copper/metabolism
  • Copper/toxicity*
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/metabolism
  • Hypoxia/metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
  • Larva
  • Oxygen/metabolism
  • Signal Transduction
  • Water Pollutants, Chemical/metabolism
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/embryology
  • Zebrafish/metabolism*
PubMed
27019216 Full text @ Env. Sci. Tech.
Abstract
Hypoxia is a global and increasingly important stressor in aquatic ecosystems, with major impacts on biodiversity worldwide. Hypoxic waters are often contaminated with a wide range of chemicals but little is known about the interactions between these stressors. We investigated the effects of hypoxia on the responses of zebrafish (Danio rerio) embryos to copper, a widespread aquatic contaminant. We showed that during continuous exposures copper toxicity was reduced by over 2-fold under hypoxia compared to normoxia. When exposures were conducted during 24h windows, hypoxia reduced copper toxicity during early development and increased its toxicity in hatched larvae. In order to investigate the role of the hypoxia signalling pathway on the suppression of copper toxicity during early development, we stabilised the hypoxia inducible factor (HIF) pathway under normoxia using a prolyl-4-hydroxylase inhibitor, dimethyloxalylglycine (DMOG) and demonstrated that HIF activation results in a strong reduction in copper toxicity. We also established that the reduction in copper toxicity during early development was independent of copper uptake, while after hatching, copper uptake was increased under hypoxia, corresponding to an increase in copper toxicity. These findings change our understanding of the current and future impacts of world-wide oxygen depletion on fish communities challenged by anthropogenic toxicants.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping