Nrf2 and Nrf2-related proteins in development and developmental toxicity : insights from studies in zebrafish (Danio rerio)
Nrf2 and Nrf2-related proteins in development and developmental toxicity : insights from studies in zebrafish (Danio rerio)
Date
2015-06-15
Authors
Hahn, Mark E.
Timme-Laragy, Alicia R.
Karchner, Sibel I.
Stegeman, John J.
Timme-Laragy, Alicia R.
Karchner, Sibel I.
Stegeman, John J.
Linked Authors
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Keywords
Oxidative stress
NRF2
NFE2L2
Embryo
Zebrafish
Development
NRF2
NFE2L2
Embryo
Zebrafish
Development
Abstract
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.
Description
© The Author(s), 2015. 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.