Nucleoredoxin Plays a Key Role in the Maintenance of Retinal Pigmented Epithelium Differentiation

Nucleoredoxin (Nrx) belongs to the Thioredoxin protein family and functions in redox-mediated signal transduction. It contains the dithiol active site motif Cys-Pro-Pro-Cys and interacts and regulates different proteins in distinct cellular pathways. Nrx was shown to be catalytically active in the i...

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Detalhes bibliográficos
Autores: Holubiec, Mariana Ines, Romero, Juan Ignacio, Urbainsky, Claudia, Gellert, Manuela, Galeano, Pablo, Capani, Francisco, Lillig, Christopher Horst, Hanschmann, Eva Maria
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/214766
Acesso em linha:http://hdl.handle.net/11336/214766
Access Level:acceso abierto
Palavra-chave:DIFFERENTIATION
GLIA
HYPOXIA-ISCHEMIA
MORPHOLOGY
NEURONS
NUCLEOREDOXIN
REDOX REGULATION
REOXYGENATION
RETINA
RPE
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Nucleoredoxin (Nrx) belongs to the Thioredoxin protein family and functions in redox-mediated signal transduction. It contains the dithiol active site motif Cys-Pro-Pro-Cys and interacts and regulates different proteins in distinct cellular pathways. Nrx was shown to be catalytically active in the insulin assay and recent findings indicate that Nrx functions, in fact, as oxidase. Here, we have analyzed Nrx in the mammalian retina exposed to (perinatal) hypoxia-ischemia/reoxygenation, combining ex vivo and in vitro models. Our data show that Nrx regulates cell differentiation, which is important to (i) increase the number of glial cells and (ii) replenish neurons that are lost following the hypoxic insult. Nrx is essential to maintain cell morphology. These regulatory changes are related to VEGF but do not seem to be linked to the Wnt/β-catenin pathway, which is not affected by Nrx knock-down. In conclusion, our results strongly suggest that hypoxia-ischemia could lead to alterations in the organization of the retina, related to changes in RPE cell differentiation. Nrx may play an essential role in the maintenance of the RPE cell differentiation state via the regulation of VEGF release.