Hypoxia suppressed copper toxicity during early development in zebrafish embryos in a process mediated by the activation of the HIF signalling pathway.
Dewar Fowler, VH
Uren Webster, TM
Environmental Science and Technology
American Chemical Society
This is the author accepted manuscript. The final version is available from American Chemical Society via the DOI in this record.
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.
This work was funded by a PhD studentship from the Centre for Environment, Fisheries and Aquaculture Science (Cefas; http://cefas.defra.gov.uk/) and the University of Exeter (http://www.exeter.ac.uk/). TMUW was funded by a Natural Environment Research Council CASE PhD studentship (grant no. NE/I528326/1) and the Salmon & Trout Association.
Published online 28 March 2016