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Free Radic Biol Med ; 81: 22-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25596499

RESUMO

Rod-derived cone viability factor (RdCVF) is a trophic factor of the thioredoxins family that promotes the survival of cone photoreceptors. It is encoded by the nucleoredoxin-like gene 1 Nxnl1 which also encodes by alternative splicing a long form of RdCVF (RdCVFL), a thioredoxin enzyme that interacts with TAU. The known role of thioredoxins in the defense mechanism against oxidative damage led us to examine the retinal phenotype of the Nxnl1(-/-) mice exposed to photooxidative stress. Here we found that, in contrast to wild-type mice, the rod photoreceptors of Nxnl1(-/-) mice are more sensitive to light after exposure to 1700 or 2500 lx. The delivery of RdCVF by AAV to mice deficient of Nxnl1(-/-) protects rod photoreceptors from light damage. Interestingly, the RdCVF2L protein, encoded by the paralog gene Nxnl2, is able to reduce TAU phosphorylation, as does RdCVFL, but does not protect the rod from light damage. Our result shows that the Nxnl1 gene, through the thioredoxin RdCVFL, is part of an endogenous defense mechanism against photooxidative stress that is likely of great importance for human vision.


Assuntos
Proteínas do Olho/genética , Terapia Genética/métodos , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Retinose Pigmentar/terapia , Tiorredoxinas/genética , Processamento Alternativo , Animais , Sobrevivência Celular , Dependovirus/genética , Proteínas do Olho/metabolismo , Feminino , Deleção de Genes , Técnicas de Transferência de Genes , Luz/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Oxirredução , Estresse Oxidativo , Fosforilação , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/patologia , Retinose Pigmentar/etiologia , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Transdução de Sinais , Tiorredoxinas/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
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