Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression
Hypoxia has been associated with several pathological conditions ranging from stroke to cancer. This condition results in the activation of autophagy, a cyto-protective response involving the formation of double-membraned structures, the autophagosomes, in the cytoplasm. In this study, we investigat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473010/ https://www.ncbi.nlm.nih.gov/pubmed/26086269 http://dx.doi.org/10.1371/journal.pone.0129750 |
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author | Pourpirali, Somayeh Valacca, Cristina Merlo, Paola Rizza, Salvatore D’Amico, Silvia Cecconi, Francesco |
author_facet | Pourpirali, Somayeh Valacca, Cristina Merlo, Paola Rizza, Salvatore D’Amico, Silvia Cecconi, Francesco |
author_sort | Pourpirali, Somayeh |
collection | PubMed |
description | Hypoxia has been associated with several pathological conditions ranging from stroke to cancer. This condition results in the activation of autophagy, a cyto-protective response involving the formation of double-membraned structures, the autophagosomes, in the cytoplasm. In this study, we investigated the cellular mechanisms regulating the autophagy gene Ambra1, after exposure to a hypoxia mimetic, cobalt chloride (CoCl(2)). We observed that, upon CoCl(2) administration, activation of the apoptotic machinery was concomitant with down-regulation of the pro-autophagic factor Ambra1, without affecting transcription. Additionally, co-treating the cells with the caspase inhibitor z-VAD-FMK did not restore Ambra1 protein levels, this implying the involvement of other regulatory mechanisms. Partial re-localization of Ambra1 mRNA to non-translating fractions and cytoplasmic P-bodies was further detected. Thus, in this pseudohypoxic context, Ambra1 mRNA translocation to P-bodies and translational suppression correlated with increased cell death. |
format | Online Article Text |
id | pubmed-4473010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44730102015-06-29 Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression Pourpirali, Somayeh Valacca, Cristina Merlo, Paola Rizza, Salvatore D’Amico, Silvia Cecconi, Francesco PLoS One Research Article Hypoxia has been associated with several pathological conditions ranging from stroke to cancer. This condition results in the activation of autophagy, a cyto-protective response involving the formation of double-membraned structures, the autophagosomes, in the cytoplasm. In this study, we investigated the cellular mechanisms regulating the autophagy gene Ambra1, after exposure to a hypoxia mimetic, cobalt chloride (CoCl(2)). We observed that, upon CoCl(2) administration, activation of the apoptotic machinery was concomitant with down-regulation of the pro-autophagic factor Ambra1, without affecting transcription. Additionally, co-treating the cells with the caspase inhibitor z-VAD-FMK did not restore Ambra1 protein levels, this implying the involvement of other regulatory mechanisms. Partial re-localization of Ambra1 mRNA to non-translating fractions and cytoplasmic P-bodies was further detected. Thus, in this pseudohypoxic context, Ambra1 mRNA translocation to P-bodies and translational suppression correlated with increased cell death. Public Library of Science 2015-06-18 /pmc/articles/PMC4473010/ /pubmed/26086269 http://dx.doi.org/10.1371/journal.pone.0129750 Text en © 2015 Pourpirali 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 Pourpirali, Somayeh Valacca, Cristina Merlo, Paola Rizza, Salvatore D’Amico, Silvia Cecconi, Francesco Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression |
title | Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression |
title_full | Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression |
title_fullStr | Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression |
title_full_unstemmed | Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression |
title_short | Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression |
title_sort | prolonged pseudohypoxia targets ambra1 mrna to p-bodies for translational repression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473010/ https://www.ncbi.nlm.nih.gov/pubmed/26086269 http://dx.doi.org/10.1371/journal.pone.0129750 |
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