Nrf2 and Nrf2-related proteins in development and developmental toxicity : insights from studies in zebrafish (Danio rerio)
Hahn, Mark E.
Timme-Laragy, Alicia R.
Karchner, Sibel I.
Stegeman, John J.
MetadataShow full item record
Oxidative stress is an important mechanism of chemical toxicity, contributing to developmental toxicity and teratogenesis as well as to cardiovascular and neurodegenerative diseases and diabetic embryopathy. Developing animals are especially sensitive to effects of chemicals that disrupt the balance of processes generating reactive species and oxidative stress, and those anti-oxidant defenses that protect against oxidative stress. The expression and inducibility of anti-oxidant defenses through activation of NFE2-related factor 2 (Nrf2) and related proteins is an essential process affecting the susceptibility to oxidants, but the complex interactions of Nrf2 in determining embryonic response to oxidants and oxidative stress are only beginning to be understood. The zebrafish (Danio rerio) is an established model in developmental biology and now also in developmental toxicology and redox signaling. Here we review the regulation of genes involved in protection against oxidative stress in developing vertebrates, with a focus on Nrf2 and related cap’n’collar (CNC)-basic-leucine zipper (bZIP) transcription factors. Vertebrate animals including zebrafish share Nfe2, Nrf1, Nrf2, and Nrf3 as well as a core set of genes that respond to oxidative stress, contributing to the value of zebrafish as a model system with which to investigate the mechanisms involved in regulation of redox signaling and the response to oxidative stress during embryolarval development. Moreover, studies in zebrafish have revealed nrf and keap1 gene duplications that provide an opportunity to dissect multiple functions of vertebrate NRF genes, including multiple sensing mechanisms involved in chemical-specific effects.
© The Author(s), [year]. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Free Radical Biology and Medicine 88B (2015): 275-289, doi:10.1016/j.freeradbiomed.2015.06.022.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States
Showing items related by title, author, creator and subject.
Buchan, Jillian G.; Gray, Ryan S.; Gansner, John M.; Alvarado, David M.; Burgert, Lydia; Gitlin, Jonathan D.; Gurnett, Christina A.; Goldsmith, Matthew I. (2014-06)Idiopathic scoliosis is a form of spinal deformity that affects 2–3% of children and results in curvature of the spine without structural defects of the vertebral units. The pathogenesis of idiopathic scoliosis remains ...
Regulation of Ahr signaling by Nrf2 during development : effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio) Rousseau, Michelle E.; Sant, Karilyn E.; Borden, Linnea R.; Franks, Diana G.; Hahn, Mark E.; Timme-Laragy, Alicia R. (2015-06)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 ...
Timme-Laragy, Alicia R.; Van Tiem, Lindsey A.; Linney, Elwood A.; Di Giulio, Richard T. (2008-12)Early piscine life-stages are sensitive to polycyclic aromatic hydrocarbon (PAH) exposure, which can cause pericardial effusion and craniofacial malformations. We previously reported that certain combinations of PAHs ...