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ER Stress in Retinal Degeneration in S334ter Rho Rats
The S334ter rhodopsin (Rho) rat (line 4) bears the rhodopsin gene with an early termination codon at residue 334 that is a model for several such mutations found in human patients with autosomal dominant retinitis pigmentosa (ADRP). The Unfolded Protein Response (UPR) is implicated in the pathophysi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303830/ https://www.ncbi.nlm.nih.gov/pubmed/22432009 http://dx.doi.org/10.1371/journal.pone.0033266 |
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author | Shinde, Vishal M. Sizova, Olga S. Lin, Jonathan H. LaVail, Matthew M. Gorbatyuk, Marina S. |
author_facet | Shinde, Vishal M. Sizova, Olga S. Lin, Jonathan H. LaVail, Matthew M. Gorbatyuk, Marina S. |
author_sort | Shinde, Vishal M. |
collection | PubMed |
description | The S334ter rhodopsin (Rho) rat (line 4) bears the rhodopsin gene with an early termination codon at residue 334 that is a model for several such mutations found in human patients with autosomal dominant retinitis pigmentosa (ADRP). The Unfolded Protein Response (UPR) is implicated in the pathophysiology of several retinal disorders including ADRP in P23H Rho rats. The aim of this study was to examine the onset of UPR gene expression in S334ter Rho retinas to determine if UPR is activated in ADRP animal models and to investigate how the activation of UPR molecules leads to the final demise of S334ter Rho photoreceptors. RT-PCR was performed to evaluate the gene expression profiles for the P10, P12, P15, and P21 stages of the development and progression of ADRP in S334ter Rho photoreceptors. We determined that during the P12–P15 period, ER stress-related genes are strongly upregulated in transgenic retinas, resulting in the activation of the UPR that was confirmed using western blot analysis and RT-PCR. The activation of UPR was associated with the increased expression of JNK, Bik, Bim, Bid, Noxa, and Puma genes and cleavage of caspase-12 that together with activated calpains presumably compromise the integrity of the mitochondrial MPTP, leading to the release of pro-apoptotic AIF1 into the cytosol of S334ter Rho photoreceptor cells. Therefore, two major cross-talking pathways, the UPR and mitochondrial MPTP occur in S334ter-4 Rho retina concomitantly and eventually promote the death of the photoreceptor cells. |
format | Online Article Text |
id | pubmed-3303830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33038302012-03-19 ER Stress in Retinal Degeneration in S334ter Rho Rats Shinde, Vishal M. Sizova, Olga S. Lin, Jonathan H. LaVail, Matthew M. Gorbatyuk, Marina S. PLoS One Research Article The S334ter rhodopsin (Rho) rat (line 4) bears the rhodopsin gene with an early termination codon at residue 334 that is a model for several such mutations found in human patients with autosomal dominant retinitis pigmentosa (ADRP). The Unfolded Protein Response (UPR) is implicated in the pathophysiology of several retinal disorders including ADRP in P23H Rho rats. The aim of this study was to examine the onset of UPR gene expression in S334ter Rho retinas to determine if UPR is activated in ADRP animal models and to investigate how the activation of UPR molecules leads to the final demise of S334ter Rho photoreceptors. RT-PCR was performed to evaluate the gene expression profiles for the P10, P12, P15, and P21 stages of the development and progression of ADRP in S334ter Rho photoreceptors. We determined that during the P12–P15 period, ER stress-related genes are strongly upregulated in transgenic retinas, resulting in the activation of the UPR that was confirmed using western blot analysis and RT-PCR. The activation of UPR was associated with the increased expression of JNK, Bik, Bim, Bid, Noxa, and Puma genes and cleavage of caspase-12 that together with activated calpains presumably compromise the integrity of the mitochondrial MPTP, leading to the release of pro-apoptotic AIF1 into the cytosol of S334ter Rho photoreceptor cells. Therefore, two major cross-talking pathways, the UPR and mitochondrial MPTP occur in S334ter-4 Rho retina concomitantly and eventually promote the death of the photoreceptor cells. Public Library of Science 2012-03-14 /pmc/articles/PMC3303830/ /pubmed/22432009 http://dx.doi.org/10.1371/journal.pone.0033266 Text en Shinde 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 Shinde, Vishal M. Sizova, Olga S. Lin, Jonathan H. LaVail, Matthew M. Gorbatyuk, Marina S. ER Stress in Retinal Degeneration in S334ter Rho Rats |
title | ER Stress in Retinal Degeneration in S334ter Rho Rats |
title_full | ER Stress in Retinal Degeneration in S334ter Rho Rats |
title_fullStr | ER Stress in Retinal Degeneration in S334ter Rho Rats |
title_full_unstemmed | ER Stress in Retinal Degeneration in S334ter Rho Rats |
title_short | ER Stress in Retinal Degeneration in S334ter Rho Rats |
title_sort | er stress in retinal degeneration in s334ter rho rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303830/ https://www.ncbi.nlm.nih.gov/pubmed/22432009 http://dx.doi.org/10.1371/journal.pone.0033266 |
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