Regulation of Ahr signaling by Nrf2 during development : effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio)
Date
2015-06Author
Rousseau, Michelle E.
Concept link
Sant, Karilyn E.
Concept link
Borden, Linnea R.
Concept link
Franks, Diana G.
Concept link
Hahn, Mark E.
Concept link
Timme-Laragy, Alicia R.
Concept link
Metadata
Show full item recordCitable URI
https://hdl.handle.net/1912/7531As published
https://doi.org/10.1016/j.aquatox.2015.08.002Keyword
Transcription factor; Dioxin-like compound; Gene expression; Embryonic development; Swim bladder; YolkAbstract
The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and
has been reported to involve oxidative stress. Ahr participates in crosstalk with another
transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the
adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr
and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding
domain in Nrf2a (nrf2afh318/fh318), rendering these embryos more sensitive to oxidative stress.
Embryos were exposed to 2 nM or 5 nM PCB126 at 24 hours post fertilization (prim-5 stage of
pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf;
protruding –mouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126
toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental
differences from wildtype embryos, including delayed inflation of the swim bladder and smaller
yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a,
keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was
enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM).
Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was
accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2,
NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1),
showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This
study elucidates the interaction between two important transcription factor pathways in the
developmental toxicity of co-planar PCBs.
Description
Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 167 (2015): 157-171, doi:10.1016/j.aquatox.2015.08.002.
Collections
Suggested Citation
Preprint: Rousseau, Michelle E., Sant, Karilyn E., Borden, Linnea R., Franks, Diana G., Hahn, Mark E., Timme-Laragy, Alicia R., "Regulation of Ahr signaling by Nrf2 during development : effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio)", 2015-06, https://doi.org/10.1016/j.aquatox.2015.08.002, https://hdl.handle.net/1912/7531Related items
Showing items related by title, author, creator and subject.
-
Fisheries library development in SADC (Southern Africa Development Community): what is the role for ALCOM?
Mashumba, Farai (IAMSLIC, 1996) -
Early Pliocene increase in thermohaline overturning : a precondition for the development of the modern equatorial Pacific cold tongue
Steph, Silke; Tiedemann, Ralf; Prange, Matthias; Groeneveld, Jeroen; Schulz, Michael; Timmermann, Axel; Nürnberg, Dirk; Ruhlemann, Carsten; Saukel, Cornelia; Haug, Gerald H. (American Geophysical Union, 2010-04-15)Unraveling the processes responsible for Earth's climate transition from an “El Niño–like state” during the warm early Pliocene into a modern-like “La Niña–dominated state” currently challenges the scientific community. ... -
A dike–groyne algorithm in a terrain-following coordinate ocean model (FVCOM) : development, validation and application
Ge, Jianzhong; Chen, Changsheng; Qi, Jianhua; Ding, Pingxing; Beardsley, Robert C. (2012-01)A dike-groyne module is developed and implemented into the unstructured-grid, three dimensional primitive equation Finite-Volume Coastal Ocean Model (FVCOM) for the study of the hydrodynamics around human-made construction ...