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Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium
In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424139/ https://www.ncbi.nlm.nih.gov/pubmed/34376625 http://dx.doi.org/10.14348/molcells.2021.0138 |
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author | Kim, You-Joung Park, Sooyeon Ha, Taejeong Kim, Seungbeom Lim, Soyeon You, Han Kim, Jin Woo |
author_facet | Kim, You-Joung Park, Sooyeon Ha, Taejeong Kim, Seungbeom Lim, Soyeon You, Han Kim, Jin Woo |
author_sort | Kim, You-Joung |
collection | PubMed |
description | In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive ROL is toxic, the RPE must also establish mechanisms to protect against ROL toxicity. Here, we found that the levels of retinol dehydrogenases (RDHs) are commonly decreased in phosphatase tensin homolog (Pten)-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that RDH gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the Pten-deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity. |
format | Online Article Text |
id | pubmed-8424139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-84241392021-09-20 Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium Kim, You-Joung Park, Sooyeon Ha, Taejeong Kim, Seungbeom Lim, Soyeon You, Han Kim, Jin Woo Mol Cells Research Article In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive ROL is toxic, the RPE must also establish mechanisms to protect against ROL toxicity. Here, we found that the levels of retinol dehydrogenases (RDHs) are commonly decreased in phosphatase tensin homolog (Pten)-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that RDH gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the Pten-deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity. Korean Society for Molecular and Cellular Biology 2021-08-31 2021-08-11 /pmc/articles/PMC8424139/ /pubmed/34376625 http://dx.doi.org/10.14348/molcells.2021.0138 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/) |
spellingShingle | Research Article Kim, You-Joung Park, Sooyeon Ha, Taejeong Kim, Seungbeom Lim, Soyeon You, Han Kim, Jin Woo Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium |
title | Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium |
title_full | Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium |
title_fullStr | Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium |
title_full_unstemmed | Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium |
title_short | Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium |
title_sort | retinoid metabolism in the degeneration of pten-deficient mouse retinal pigment epithelium |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424139/ https://www.ncbi.nlm.nih.gov/pubmed/34376625 http://dx.doi.org/10.14348/molcells.2021.0138 |
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