PUBLICATION
Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging
- Authors
- Xu, H., Jiang, Y., Li, S., Xie, L., Tao, Y.X., Li, Y.
- ID
- ZDB-PUB-201002-197
- Date
- 2020
- Source
- Genes 11(10): (Journal)
- Registered Authors
- Li, Yun, Xu, Hao
- Keywords
- Oxr1a, aging, antioxidant defenses, apoptosis, oxidative stress, p53 signaling pathway, vertebrates, zebrafish
- MeSH Terms
-
- Animals
- Antioxidants/metabolism*
- Apoptosis
- CRISPR-Cas Systems*
- Longevity*
- Mutation
- Oxidative Stress*
- Reactive Oxygen Species/metabolism
- Reproduction*
- Signal Transduction
- Transcriptome*
- Zebrafish
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32987694 Full text @ Genes (Basel)
Citation
Xu, H., Jiang, Y., Li, S., Xie, L., Tao, Y.X., Li, Y. (2020) Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging. Genes. 11(10):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping