PUBLICATION

Paraquat affects mitochondrial bioenergetics, dopamine system expression, and locomotor activity in zebrafish (Danio rerio)

Authors
Wang, X.H., Souders, C.L., Zhao, Y.H., Martyniuk, C.J.
ID
ZDB-PUB-171017-10
Date
2017
Source
Chemosphere   191: 106-117 (Journal)
Registered Authors
Keywords
Behavior, Dopaminergic signaling, Mitochondrial respiration, Oxidative stress, Paraquat
MeSH Terms
  • Animals
  • Dopamine/genetics
  • Dopamine/metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Energy Metabolism
  • Herbicides/metabolism
  • Herbicides/toxicity*
  • Larva/metabolism
  • Locomotion/drug effects*
  • Mitochondria/metabolism*
  • Oxidative Stress/drug effects
  • Paraquat/toxicity*
  • Superoxide Dismutase
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • bcl-2-Associated X Protein/metabolism
PubMed
29031050 Full text @ Chemosphere
CTD
29031050
Abstract
The dipyridyl herbicide paraquat induces oxidative stress in cells and is implicated in adult neurodegenerative diseases. However, less is known about paraquat toxicity in early stages of vertebrate development. To address this gap, zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 μM paraquat for 96 h. Paraquat did not induce significant mortality nor deformity in embryos and larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial respiration was related to earlier hatch times, oxygen consumption rate was measured in whole embryos. Maximal respiration of embryos exposed to 100 μM paraquat for 24 h was reduced by more than 70%, suggesting that paraquat negatively impacts mitochondrial bioenergetics in early development. Based upon this evidence for mitochondrial dysfunction, transcriptional responses of oxidative stress- and apoptosis-related genes were measured. Fish exposed to 1 μM paraquat showed higher expression levels of superoxide dismutase 2, heat shock protein 70, Bcl-2-associated X protein, and B-cell CLL/lymphoma 2a compared to control fish. No differences among groups were detected in larvae exposed to 10 and 100 μM paraquat, suggesting a non-monotonic response. We also measured endpoints related to larval behavior and dopaminergic signaling as paraquat is associated with degeneration of dopamine neurons. Locomotor activity was stimulated with 100 μM paraquat and dopamine transporter and dopamine receptor 3 mRNA levels were increased in larvae exposed to 1 μM paraquat, interpreted to be a compensatory response at lower concentrations. This study improves mechanistic understanding into the toxic actions of paraquat on early developmental stages.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping