Up-regulation of P-gp via NF-κB activation confers protection against oxidative damage in the retinal pigment epithelium cells.
Exp Eye Res
; 181: 367-373, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30496729
ABSTRACT
Dysfunction of retinal pigment epithelial (RPE) cells has been associated with the pathogenesis of age-related macular degeneration in relation to increased oxidative stress, subsequent mitochondrial dysfunction and cell death. Permeability-glycoprotein (P-gp), encoded by the multidrug resistance 1 gene (MDR1), is an active efflux pump involved in cell homeostasis and nuclear factor κB (NF-κB) shows potential involvement in P-gp regulation due to its binding to the promoter domains of MDR1 gene. This study sought to determine the role of P-gp expression regulated by NF-κB in RPE cells during oxidative stress. The human RPE D407â¯cells were exposed to increasing concentrations of hydrogen peroxide (H2O2) for 24â¯h. The small-interfering RNA (siRNA) transfection was used to down-regulate P-gp and NF-κB, and the expressions of P-gp and NF-κB p65 were determined by quantitative real-time PCR, western blot and immunofluorescence. The activity of NF-κB was detected by luciferase reporter assay. Mitochondrial membrane potential and cell death rate were detected by flow cytometry. We found that H2O2 exposure caused increasing rate of cell death and induced an elevated expression of P-gp as well as NF-κB activation and nucleus translocation in D407â¯cells. Inhibiting or silencing NF-κB led to a decrease in the oxidative-induced expression of P-gp. Down-regulation of P-gp by siRNA transfection further impaired the mitochondrial membrane potential and cell death rate in oxidative cells. Moreover, inhibition/knockdown of NF-κB decreased the high rate of cell death caused by H2O2. In conclusion, P-gp can provide moderate cytoprotection for the human RPE cells by ameliorating the mitochondrial dysfunction and NF-κB activation may be a potential regulator of P-gp expression response to oxidative stress.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
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Regulação para Cima
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NF-kappa B
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Estresse Oxidativo
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Epitélio Pigmentado da Retina
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Degeneração Macular
Limite:
Humans
Idioma:
En
Revista:
Exp Eye Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China