Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells.
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 RP...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0271656 |
| _version_ | 1818483415957110784 |
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| author | YongYao Xu Michael Twarog Ning Li Angela Banks Josh Schustak Yi Bao Qian Huang Quintus G Medley |
| author_facet | YongYao Xu Michael Twarog Ning Li Angela Banks Josh Schustak Yi Bao Qian Huang Quintus G Medley |
| author_sort | YongYao Xu |
| collection | DOAJ |
| description | 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-1β/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 β /TNF- α despite Zip7 inhibition. A cell permeable Zn chelator demonstrated that Zn is essential for IL-1 β /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 β /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. |
| first_indexed | 2024-12-10T15:41:45Z |
| format | Article |
| id | doaj.art-ff73794092cd40c7aa5e86812b8f2d2c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T15:41:45Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ff73794092cd40c7aa5e86812b8f2d2c2022-12-22T01:43:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01177e027165610.1371/journal.pone.0271656Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells.YongYao XuMichael TwarogNing LiAngela BanksJosh SchustakYi BaoQian HuangQuintus G MedleyInflammatory 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-1β/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 β /TNF- α despite Zip7 inhibition. A cell permeable Zn chelator demonstrated that Zn is essential for IL-1 β /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 β /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.https://doi.org/10.1371/journal.pone.0271656 |
| spellingShingle | YongYao Xu Michael Twarog Ning Li Angela Banks Josh Schustak Yi Bao Qian Huang Quintus G Medley 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 |
| title | Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells. |
| title_full | Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells. |
| title_fullStr | Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells. |
| title_full_unstemmed | Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells. |
| title_short | Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells. |
| title_sort | zinc transport from the endoplasmic reticulum to the cytoplasm via zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in rpe cells |
| url | https://doi.org/10.1371/journal.pone.0271656 |
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