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X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium

Damage to the retinal pigment epithelium (RPE) is an early event in the pathogenesis of age-related macular degeneration (AMD). X-box binding protein 1 (XBP1) is a key transcription factor that regulates endoplasmic reticulum (ER) homeostasis and cell survival. This study aimed to delineate the role...

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Autores principales: Zhong, Yimin, Li, Jingming, Wang, Joshua J., Chen, Chen, Tran, Julie-Thu A., Saadi, Anisse, Yu, Qiang, Le, Yun-zheng, Mandal, Md Nawajes A., Anderson, Robert E., Zhang, Sarah X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371004/
https://www.ncbi.nlm.nih.gov/pubmed/22715395
http://dx.doi.org/10.1371/journal.pone.0038616
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author Zhong, Yimin
Li, Jingming
Wang, Joshua J.
Chen, Chen
Tran, Julie-Thu A.
Saadi, Anisse
Yu, Qiang
Le, Yun-zheng
Mandal, Md Nawajes A.
Anderson, Robert E.
Zhang, Sarah X.
author_facet Zhong, Yimin
Li, Jingming
Wang, Joshua J.
Chen, Chen
Tran, Julie-Thu A.
Saadi, Anisse
Yu, Qiang
Le, Yun-zheng
Mandal, Md Nawajes A.
Anderson, Robert E.
Zhang, Sarah X.
author_sort Zhong, Yimin
collection PubMed
description Damage to the retinal pigment epithelium (RPE) is an early event in the pathogenesis of age-related macular degeneration (AMD). X-box binding protein 1 (XBP1) is a key transcription factor that regulates endoplasmic reticulum (ER) homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD.
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spelling pubmed-33710042012-06-19 X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium Zhong, Yimin Li, Jingming Wang, Joshua J. Chen, Chen Tran, Julie-Thu A. Saadi, Anisse Yu, Qiang Le, Yun-zheng Mandal, Md Nawajes A. Anderson, Robert E. Zhang, Sarah X. PLoS One Research Article Damage to the retinal pigment epithelium (RPE) is an early event in the pathogenesis of age-related macular degeneration (AMD). X-box binding protein 1 (XBP1) is a key transcription factor that regulates endoplasmic reticulum (ER) homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD. Public Library of Science 2012-06-08 /pmc/articles/PMC3371004/ /pubmed/22715395 http://dx.doi.org/10.1371/journal.pone.0038616 Text en Zhong et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhong, Yimin
Li, Jingming
Wang, Joshua J.
Chen, Chen
Tran, Julie-Thu A.
Saadi, Anisse
Yu, Qiang
Le, Yun-zheng
Mandal, Md Nawajes A.
Anderson, Robert E.
Zhang, Sarah X.
X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium
title X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium
title_full X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium
title_fullStr X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium
title_full_unstemmed X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium
title_short X-Box Binding Protein 1 Is Essential for the Anti-Oxidant Defense and Cell Survival in the Retinal Pigment Epithelium
title_sort x-box binding protein 1 is essential for the anti-oxidant defense and cell survival in the retinal pigment epithelium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371004/
https://www.ncbi.nlm.nih.gov/pubmed/22715395
http://dx.doi.org/10.1371/journal.pone.0038616
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