Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells.
PLoS One
; 17(7): e0271656, 2022.
Article
em En
| MEDLINE
| ID: mdl-35901031
ABSTRACT
Inflammatory signaling induces barrier dysfunction in retinal-pigmented epithelium (RPE) cells and plays a role in the pathology of age-related macular degeneration (AMD). We studied the role of Zn flux from the endoplasmic reticulum (ER) to the cytoplasm via Zip7 during inflammatory signaling in RPE cells. In ARPE-19 cells, Zip7 inhibition reduced impedance loss, FITC-dextran permeability and cytokine induction caused by challenge with IL-1ß/TNF-α. Zip7 inhibition in iPS-derived RPE cells challenged with TNF- α reduced barrier loss in TER assays. In ARPE-19 cells, a Zn ionophore restored cytokine induction and barrier loss in cells challenged with IL-1 ß /TNF- α despite Zip7 inhibition. A cell permeable Zn chelator demonstrated that Zn is essential for IL-1 ß /TNF- α signaling. ER stress caused by Zip7 inhibition in ARPE-19 cells was found to partially contribute to reducing barrier dysfunction caused by IL-1 ß /TNF- α. Overall, it was shown that Zn flux through Zip7 from the ER to the cytoplasm plays a critical role in driving barrier dysfunction caused by inflammatory cytokines in RPE cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte de Cátions
/
Retículo Endoplasmático
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos