Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium
| Autor: | Sooyeon Park, You-Joung Kim, Jin Woo Kim, Taejeong Ha, Seungbeom Kim, Han You, Soyeon Lim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
retinoids
retinal pigment epithelium Mice Transgenic phosphoinositide 3-kinase-Akt pathway Gene expression medicine Tensin PTEN Animals Vitamin A Molecular Biology Protein kinase B Transcription factor Retina Retinal pigment epithelium biology Chemistry Retinal Degeneration PTEN Phosphohydrolase phosphatase tensin homolog Forkhead Transcription Factors Cell Biology General Medicine Aldehyde Dehydrogenase eye diseases Cell biology Diet Alcohol Oxidoreductases medicine.anatomical_structure RPE65 biology.protein forkhead box O sense organs Research Article |
| Zdroj: | Molecules and Cells |
| ISSN: | 0219-1032 1016-8478 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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