Nrf2 and Nrf2-related proteins in development and developmental toxicity: Insights from studies in zebrafish (Danio rerio) |
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| Affiliation: | 1. Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts, United States of America;2. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America;1. King’s College London, UK;2. University of California-Merced, USA;3. Tohoku University, Japan;4. University of Pittsburgh, USA;5. University of Dundee, UK;1. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, United States;2. Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, United States;1. Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China;2. Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China;3. Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan, China;1. State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;4. State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China;1. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA;2. Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA;3. Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA;4. Molecular & Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA 01003, USA;5. Biotechnology Training Program, University of Massachusetts, Amherst, MA 01003, USA;1. Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Key Laboratory for Biosensor of Shandong Province, Jinan, Shandong Province, PR China;2. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, Henan Province, PR China;3. Beijing 302 Hospital of China, Beijing, PR China;4. College of Pharmacy, Henan University, Kaifeng, Henan Province, PR China;5. Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan |
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| 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. |
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| Keywords: | Oxidative stress Nrf2 NFE2L2 Embryo Zebrafish Development |
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