Deletion of narfl leads to increased oxidative stress mediated abnormal angiogenesis and digestive organ defects in zebrafish.
Redox Biol
; 28: 101355, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31677554
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Peixe-Zebra
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Trato Gastrointestinal
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Técnicas de Inativação de Genes
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Proteínas Ferro-Enxofre
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Redox Biol
Ano de publicação:
2020
Tipo de documento:
Article