PUBLICATION
Deletion of narfl leads to increased oxidative stress mediated abnormal angiogenesis and digestive organ defects in zebrafish
- Authors
- Luo, J., Zhang, X., He, S., Lou, Q., Zhai, G., Shi, C., Yin, Z., Zheng, F.
- ID
- ZDB-PUB-191106-7
- Date
- 2019
- Source
- Redox Biology 28: 101355 (Journal)
- Registered Authors
- Zheng, Fang
- Keywords
- Angiogenesis, Narfl, Oxidative stress, Zebrafish
- MeSH Terms
-
- 2-Methoxyestradiol/pharmacology
- Animals
- Disease Models, Animal
- Embryonic Development/drug effects
- Gastrointestinal Tract/abnormalities*
- Gene Expression Regulation, Developmental
- Gene Knockout Techniques*
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
- Iron-Sulfur Proteins/genetics*
- Neovascularization, Pathologic/genetics*
- Oxidative Stress
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 31677554 Full text @ Redox Biol.
Citation
Luo, J., Zhang, X., He, S., Lou, Q., Zhai, G., Shi, C., Yin, Z., Zheng, F. (2019) Deletion of narfl leads to increased oxidative stress mediated abnormal angiogenesis and digestive organ defects in zebrafish. Redox Biology. 28:101355.
Abstract
Nuclear prelamin A recognition factor-like (NARFL) is a human protein that participates in cytosolic iron-sulfur (Fe-S) protein biogenesis and cellular defense against oxidative stress. Previous studies of Narfl knockout mice did not reveal well the regulatory mechanisms of embryonic development mediated by Narfl because the homozygous mice die in utero. Here, we investigated the function of narfl in an established zebrafish knockout model by taking advantage of zebrafish external fertilization and ease of embryonic development examination. Our experiments showed that narfl deletion resulted in larvae lethality, subintestinal vessel (SIV) malformation and digestive organ defects in the early stages of embryonic development. Biochemical analyses and western blot revealed increased oxidative stress and upregulated hypoxia-inducible factor-1α (HIF-1α) expression in narfl-/- fish. The use of HIF-1α inhibitor 2-methoxyestradiol (2ME2) for the treatment of mutants partially rescued the SIV sprouting. These results suggest that narfl deletion causes increased oxidative stress and subintestinal vessel malformation, which further influence the development of digestive organs and might contribute to the lethality of the narfl knockout fish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping