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Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging
Oxidation resistance gene 1 (OXR1) is essential for protection against oxidative stress in mammals, but its functions in non-mammalian vertebrates, especially in fish, remain uncertain. Here, we created a homozygous oxr1a-knockout zebrafish via the CRISPR/Cas9 (Clustered Regularly Interspaced Short...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598701/ https://www.ncbi.nlm.nih.gov/pubmed/32987694 http://dx.doi.org/10.3390/genes11101118 |
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author | Xu, Hao Jiang, Yu Li, Sheng Xie, Lang Tao, Yi-Xi Li, Yun |
author_facet | Xu, Hao Jiang, Yu Li, Sheng Xie, Lang Tao, Yi-Xi Li, Yun |
author_sort | Xu, Hao |
collection | PubMed |
description | Oxidation resistance gene 1 (OXR1) is essential for protection against oxidative stress in mammals, but its functions in non-mammalian vertebrates, especially in fish, remain uncertain. Here, we created a homozygous oxr1a-knockout zebrafish via the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9) system. Compared with wild-type (WT) zebrafish, oxr1a(−/−) mutants exhibited higher mortality and more apoptotic cells under oxidative stress, and multiple antioxidant genes (i.e., gpx1b, gpx4a, gpx7 and sod3a) involved in detoxifying cellular reactive oxygen species were downregulated significantly. Based on these observations, we conducted a comparative transcriptome analysis of early oxidative stress response. The results show that oxr1a mutation caused more extensive changes in transcriptional networks compared to WT zebrafish, and several stress response and pro-inflammatory pathways in oxr1a(−/−) mutant zebrafish were strongly induced. More importantly, we only observed the activation of the p53 signaling and apoptosis pathway in oxr1a(−/−) mutant zebrafish, revealing an important role of oxr1a in regulating apoptosis via the p53 signaling pathway. Additionally, we found that oxr1a mutation displayed a shortened lifespan and premature ovarian failure in prolonged observation, which may be caused by the loss of oxr1a impaired antioxidant defenses, thereby increasing pro-apoptotic events. Altogether, our findings demonstrate that oxr1a is vital for antioxidant defenses and anti-aging in zebrafish. |
format | Online Article Text |
id | pubmed-7598701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75987012020-10-31 Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging Xu, Hao Jiang, Yu Li, Sheng Xie, Lang Tao, Yi-Xi Li, Yun Genes (Basel) Article Oxidation resistance gene 1 (OXR1) is essential for protection against oxidative stress in mammals, but its functions in non-mammalian vertebrates, especially in fish, remain uncertain. Here, we created a homozygous oxr1a-knockout zebrafish via the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9) system. Compared with wild-type (WT) zebrafish, oxr1a(−/−) mutants exhibited higher mortality and more apoptotic cells under oxidative stress, and multiple antioxidant genes (i.e., gpx1b, gpx4a, gpx7 and sod3a) involved in detoxifying cellular reactive oxygen species were downregulated significantly. Based on these observations, we conducted a comparative transcriptome analysis of early oxidative stress response. The results show that oxr1a mutation caused more extensive changes in transcriptional networks compared to WT zebrafish, and several stress response and pro-inflammatory pathways in oxr1a(−/−) mutant zebrafish were strongly induced. More importantly, we only observed the activation of the p53 signaling and apoptosis pathway in oxr1a(−/−) mutant zebrafish, revealing an important role of oxr1a in regulating apoptosis via the p53 signaling pathway. Additionally, we found that oxr1a mutation displayed a shortened lifespan and premature ovarian failure in prolonged observation, which may be caused by the loss of oxr1a impaired antioxidant defenses, thereby increasing pro-apoptotic events. Altogether, our findings demonstrate that oxr1a is vital for antioxidant defenses and anti-aging in zebrafish. MDPI 2020-09-24 /pmc/articles/PMC7598701/ /pubmed/32987694 http://dx.doi.org/10.3390/genes11101118 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xu, Hao Jiang, Yu Li, Sheng Xie, Lang Tao, Yi-Xi Li, Yun Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging |
title | Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging |
title_full | Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging |
title_fullStr | Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging |
title_full_unstemmed | Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging |
title_short | Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging |
title_sort | zebrafish oxr1a knockout reveals its role in regulating antioxidant defenses and aging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598701/ https://www.ncbi.nlm.nih.gov/pubmed/32987694 http://dx.doi.org/10.3390/genes11101118 |
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