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Somatostatin protects photoreceptor cells against high glucose–induced apoptosis
PURPOSE: Many cellular and molecular studies in experimental animals and early retinal function tests in patients with diabetic retinopathy (DR) have shown that retinal neurodegeneration is an early event in the pathogenesis of the disease. Somatostatin (SST) is one of the most important neuroprotec...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Vision
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204461/ https://www.ncbi.nlm.nih.gov/pubmed/28050125 |
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author | Arroba, Ana I. Mazzeo, Aurora Cazzoni, Daniele Beltramo, Elena Hernández, Cristina Porta, Massimo Simó, Rafael Valverde, Ángela M. |
author_facet | Arroba, Ana I. Mazzeo, Aurora Cazzoni, Daniele Beltramo, Elena Hernández, Cristina Porta, Massimo Simó, Rafael Valverde, Ángela M. |
author_sort | Arroba, Ana I. |
collection | PubMed |
description | PURPOSE: Many cellular and molecular studies in experimental animals and early retinal function tests in patients with diabetic retinopathy (DR) have shown that retinal neurodegeneration is an early event in the pathogenesis of the disease. Somatostatin (SST) is one of the most important neuroprotective factors synthesized by the retina: SST levels are decreased in parallel to retinal neurodegeneration in early stages of DR. In this study, we characterized the induction of apoptosis (programmed cell death) in a 661W photoreceptor-like cell line cultured under high glucose (HG) conditions and the effect of SST. METHODS: A 661W photoreceptor-like cell line and retinal explants from 10-week-old male C57BL/6 mice were cultured under HG conditions and treated with SST. RESULTS: Hyperglycemia significantly reduced the cellular viability by increasing the percentage of apoptotic cells, and this effect was ameliorated by SST (p˂0.05). Activation of caspase-8 by hyperglycemia was found in the 661W cells and retinal explants and decreased in the presence of SST (p˂0.05). Moreover, we detected activation of calpain-2 associated with hyperglycemia-induced cell death, as well as increased protein tyrosine phosphatase 1B (PTP1B) protein levels; both had a pattern of cleavage that was absent in the presence of SST (p˂0.05). Treatment of the 661W cells and retinal explants with SST for 24 h increased the phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR; tyrosine 1165/1166) and protein kinase B (Akt; serine 473), suggesting this survival signaling is activated in the neuroretina by SST (p˂0.05). CONCLUSIONS: This study has provided new mechanistic insights first into the involvement of calpain-2 and PTP1B in the loss of cell survival and increased caspase-8-dependent apoptosis induced by hyperglycemia in photoreceptor cells and second, on the protective effect of SST against apoptosis by the enhancement of IGF-IR-mediated Akt phosphorylation. |
format | Online Article Text |
id | pubmed-5204461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
spelling | pubmed-52044612017-01-03 Somatostatin protects photoreceptor cells against high glucose–induced apoptosis Arroba, Ana I. Mazzeo, Aurora Cazzoni, Daniele Beltramo, Elena Hernández, Cristina Porta, Massimo Simó, Rafael Valverde, Ángela M. Mol Vis Research Article PURPOSE: Many cellular and molecular studies in experimental animals and early retinal function tests in patients with diabetic retinopathy (DR) have shown that retinal neurodegeneration is an early event in the pathogenesis of the disease. Somatostatin (SST) is one of the most important neuroprotective factors synthesized by the retina: SST levels are decreased in parallel to retinal neurodegeneration in early stages of DR. In this study, we characterized the induction of apoptosis (programmed cell death) in a 661W photoreceptor-like cell line cultured under high glucose (HG) conditions and the effect of SST. METHODS: A 661W photoreceptor-like cell line and retinal explants from 10-week-old male C57BL/6 mice were cultured under HG conditions and treated with SST. RESULTS: Hyperglycemia significantly reduced the cellular viability by increasing the percentage of apoptotic cells, and this effect was ameliorated by SST (p˂0.05). Activation of caspase-8 by hyperglycemia was found in the 661W cells and retinal explants and decreased in the presence of SST (p˂0.05). Moreover, we detected activation of calpain-2 associated with hyperglycemia-induced cell death, as well as increased protein tyrosine phosphatase 1B (PTP1B) protein levels; both had a pattern of cleavage that was absent in the presence of SST (p˂0.05). Treatment of the 661W cells and retinal explants with SST for 24 h increased the phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR; tyrosine 1165/1166) and protein kinase B (Akt; serine 473), suggesting this survival signaling is activated in the neuroretina by SST (p˂0.05). CONCLUSIONS: This study has provided new mechanistic insights first into the involvement of calpain-2 and PTP1B in the loss of cell survival and increased caspase-8-dependent apoptosis induced by hyperglycemia in photoreceptor cells and second, on the protective effect of SST against apoptosis by the enhancement of IGF-IR-mediated Akt phosphorylation. Molecular Vision 2016-12-30 /pmc/articles/PMC5204461/ /pubmed/28050125 Text en Copyright © 2016 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ 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 work is properly cited, used for non-commercial purposes, and is not altered or transformed. |
spellingShingle | Research Article Arroba, Ana I. Mazzeo, Aurora Cazzoni, Daniele Beltramo, Elena Hernández, Cristina Porta, Massimo Simó, Rafael Valverde, Ángela M. Somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
title | Somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
title_full | Somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
title_fullStr | Somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
title_full_unstemmed | Somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
title_short | Somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
title_sort | somatostatin protects photoreceptor cells against high glucose–induced apoptosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204461/ https://www.ncbi.nlm.nih.gov/pubmed/28050125 |
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