title: Hypoxia Suppressed Copper Toxicity during Early Development in Zebrafish Embryos in a Process Mediated by the Activation of the HIF Signaling Pathway.
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 24 h windows, hypoxia reduced copper toxicity during early development and increased its toxicity in hatched larvae. To investigate the role of the hypoxia signaling pathway on the suppression of copper toxicity during early development, we stabilized 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 worldwide oxygen depletion on fish communities challenged by anthropogenic toxicants.
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.|Centre for Environment, Fisheries and Aquaculture Science , Barrack Road, The Nothe, Weymouth, Dorset DT4 8UB, United Kingdom.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Fitzgerald
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jameson
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Victoria H Dewar
authors.initials: VH
authors.lastname: Fowler
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Georgia L
authors.initials: GL
authors.lastname: Bond
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Bickley
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Tamsyn M Uren
authors.initials: TM
authors.lastname: Webster
authors.affiliation: King's College London , 83 Franklin-Wilkins Building, London SE1 9NH, United Kingdom.
authors.forename: Nic R
authors.initials: NR
authors.lastname: Bury
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilson
authors.affiliation: Biosciences, College of Life & Environmental Sciences, University of Exeter , Geoffrey Pope Building, Exeter EX4 4QD, United Kingdom.
authors.forename: Eduarda M
authors.initials: EM
authors.lastname: Santos
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007814:Larva; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*
chemical_list: D000600:Amino Acids, Dicarboxylic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014874:Water Pollutants, Chemical; D003300:Copper; D010100:Oxygen; C040947:oxalylglycine